Novel Detection of Pleomorphic Adenomas via Analysis of 68Ga-DOTATOC PET/CT Imaging.

INTRODUCTION: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. METHODS: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. RESULTS: Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a 68Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). CONCLUSIONS: A strong tracer uptake in PA was shown in 68Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues.

Novel Discovery of the Somatostatin Receptor (SSTR2) in Pleomorphic Adenomas via Immunohistochemical Analysis of Tumors of the Salivary Glands.

Reliable preoperative diagnosis between salivary gland tumor entities is difficult. In this monocentric retrospective study, we examined the somatostatin receptor 2 (SSTR2) status of salivary gland tumors after salivary gland tumor resection via immunohistochemistry (IHC), and stains were compared in analogy to the HER2 mamma scale. A total of 42.3% of all pleomorphic adenoma (PA) tumors (42 of 99, 95% confidence interval 32.5-52.8%) demonstrated ≥20% of cells displaying the SSTR2 as compared to just 1% of all other tumors (1/160, 95% CI 0.02-3.4%). The other tumor was a neuroendocrine carcinoma. PA had a higher intensity of SSTR2 staining, with 90.9% staining ≥ an intensity of 2 (moderate). Tumors with an intensity of SSTR2 expression equal to or greater than 2 had an 89.9% likelihood of being a PA (95% CI: 82.2-95.0%, AUC: 0.928). Only one Warthin tumor demonstrated a 'strong' SSTR2 staining intensity. No Warthin tumor showed a percentage of cells staining for SSTR2 above ≥20%. This result demonstrates consistent and strong expression of SSTR2 in PAs as compared to Warthin tumors, which may allow physicians to utilize radioligand-somatostatin analog PET CT/MR imaging to diagnose the PA. SSTR2 positivity, if shown to be clinically relevant, may allow peptide receptor radionuclide therapy in the future.

[Laryngeal-preservation surgery in laryngeal cancer]. / Kehlkopferhaltende Operationen bei Larynxkarzinomen.

After oral cavity and pharyngeal cancer, laryngeal cancer is the third most common malignant tumor in the head and neck region. According to the current German S3 guideline on the diagnosis, treatment, and follow-up of laryngeal cancer, larynx-preserving surgical interventions are part of the standard treatment of this disease, even in advanced tumor stages. However, in order to achieve the desired function-preserving effect, an exact indication is of crucial importance. In this article, the most important larynx-preserving interventions and their indications but also the respective contraindications are presented, with the aim of illuminating the surgical treatment options up to just before total laryngectomy.

Persisting sicca complaints in sarcoidosis.

Background: Sarcoidosis is a systemic inflammatory disease that is characterized by non-caseating granulomas. Besides the lung as classical site of involvement, extrapulmonary manifestations are common, for example cervical lymph nodes or the salivary glands. The aim of this investigation is the analysis of the long-term course of glandular symptoms with a focus on persisting sicca symptoms. Materials and methods: All patients with the diagnosis of sarcoidosis over a period of 20 years in the departments of otorhinolaryngology, nephrology and pneumology were identified. In addition to clinical examinations and functional evaluation of the salivary glands, a sonographic examination of the salivary glands was carried out. Results: A total of 76 patients were included in the study (age 35.1 ± 21.6 years). At baseline, 32 out of 76 patients were suffering from xerostomia, 36 from dry eyes. While other salivary gland symptoms, such as gland enlargement, pain or facial nerve impairment, dissolved during the further course of the disease, xerostomia was still present in 29 and dry eyes in 35 out of 76 patients at the time of follow-up (which took place on average after 88.2 months). Conclusion: Sicca symptoms persist in patients with the diagnosis of sarcoidosis, while other salivary gland symptoms completely dissolve during the further course of the disease. This development appears to be independent of the type of therapy and should be considered during the follow-up of these patients, since sicca symptoms can cause further ocular, oral and dental damage.

Pre-operative cellular dissociation grading in biopsies is highly predictive of post-operative tumour stage and patient outcome in head and neck squamous cell carcinoma.

BACKGROUND: Pre-operative treatment planning in head and neck squamous cell carcinoma (HNSCC) is mainly dictated by clinical staging, which has major shortcomings. Histologic grading is irrelevant due to its lack of prognostic impact. Recently, a novel grading termed Cellular Dissociation Grade (CDG) based on Tumour Budding and Cell Nest Size was shown to be highly prognostic for resected HNSCC. We aimed to probe the predictive and prognostic impact of CDG in the pre-operative biopsies of HNSCC. METHODS: We evaluated CDG in n = 160 pre-therapeutic biopsies from patients who received standardised treatment following German guidelines, and correlated the results with pre- and post-therapeutic staging data and clinical outcome. RESULTS: Pre-operative CDG was highly predictive of post-operative tumour stage, including the prediction of occult lymph node metastasis. Uni- and multivariate analysis revealed CDG to be an independent prognosticator of overall, disease-specific and disease-free survival (p < 0.001). Hazard ratio for disease-specific survival was 6.1 (11.1) for nG2 (nG3) compared with nG1 tumours. CONCLUSIONS: CDG is a strong outcome predictor in the pre-treatment scenario of HNSCC and identifies patients with nodal-negative disease. CDG is a purely histology-based prognosticator in the pre-therapeutic setting that supplements clinical staging and may aide therapeutic stratification of HNSCC patients.

Radiofrequency resection in oral and oropharyngeal tumor surgery.

OBJECTIVE: Various techniques are available for the transoral resection of oral and oropharyngeal tumors. The application of radiofrequency proved successful in the resection of pathologies and achieved a good combination of radicality and hemostasis. The objective of this case series it to evaluate the feasibility of radiofrequency-assisted resection of oral and oropharyngeal tumors. METHODS: Patients presenting with oral or oropharyngeal tumors eligible for transoral resection were included. The excision was performed with a 4 MHz microsurgical radiofrequency generator using a monopolar needle. Radiofrequency was evaluated with perioperative (bleeding, tissue sticking, coagulation), objective (wound healing, complications) and subjective postoperative parameters (visual analogue scale of pain, impaired food intake, impaired speak). The surgical specimens were examined regarding entity, width of coagulation margins and the quality of the resection margins and compared to laser-assisted resected specimen. RESULTS: Twenty-five patients were included. 13 patients suffered from benign and 12 patients from malign lesions. Intraoperative bleeding was described as self-limiting in most of the cases and only in some cases the application of additional light pressure was required. Intraoperative tissue sticking was described as none or as resolvable by activation of the radiofrequency generator. Coagulation was limited to the area of resection. No impairment of wound healing or postoperative complications could be observed. Pain, impaired food intake and speak declined steadily. Radiofrequency-assisted resected specimen showed better assessability compared to laser-assisted resected specimen (p < 0.001). Resection margins were predominantly smooth. The width of the coagulation zones was 1593.75 µm on average. CONCLUSION: Radiofrequency is a suitable tool for the resection of oral and oropharyngeal tumors with a favourable intraoperative performance regarding the peri-incisional bleeding control and a continuous decline of postoperative morbidity.

Bradykinin Receptor B1 and C-Reactive Protein as Prognostic Factors for Pharyngocutaneous Fistula Development After Laryngectomy.

Pharyngocutaneous fistulae (PCF) are one of the most common complications after laryngectomy. Predisposing risk factors have been studied, yet knowledge to determine which patients are prone to developing a fistula remains scarce. This study aims to establish prognostic parameters to identify individual patients at risk for PCF development. As PCF and inflammation seem to be interwoven, this work focuses on markers able to detect an inflammatory response. We retrospectively analyzed all patients who had undergone a laryngectomy at our clinic in the years 2007 to 2017 (n = 182). Immunohistochemical expression of bradykinin type 1 and 2 receptor and vascular endothelial growth factor receptor 2 was studied in all available tumor samples. Additionally, the clinical inflammation parameters 'body temperature', 'pain', 'c-reactive protein (CRP)', and 'leucocytes' were postoperatively tracked in all patients. The times between fistula diagnosis, therapeutic approach, and hospital discharge were recorded. We found a strong correlation between inflammation and the formation of a fistula. High bradykinin 1 receptor expression in the tumor samples correlated with postoperative PCF development. Persistently elevated CRP and leukocyte levels beyond the 6th postoperative day were also risk factors. A decreased time lapse between PCF diagnosis and surgical revision clearly correlated with a shorter hospital stay. In this study, we identified a bradykinin 1 receptor positive patient group at high risk for development of PCF. We recommend close monitoring for fistula formation in these patients to ensure timely intervention.

Tumor Budding and Cell Nest Size Are Highly Prognostic in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: Further Evidence for a Unified Histopathologic Grading System for Squamous Cell Carcinomas of the Upper Aerodigestive Tract.

Squamous cell carcinoma (SCC) is the most common cancer of the head and neck region including-among others-laryngeal (LSCC) and hypopharyngeal (HSCC) subsites. LSCC/HSCC are heterogenous diseases with respect to patient outcome. Currently, tumor stage-based patient stratification is essential to predict prognosis and thus selection of the appropriate treatment modalities. In contrast, the prognostic impact of the current HSCC/LSCC grading system according to the WHO classification is limited. Recently, a novel grading system based on tumor budding activity (BA) and cell nest size (CNS) has been introduced for SCC in different anatomic regions of the upper aerodigestive tract. To test and transvalidate this grading scheme in LSCC and HSCC, we retrospectively correlated BA, CNS, and additional histomorphologic parameters with clinicopathologic data of 157 treatment-naive patients. In doing so, we demonstrate that a 3-tiered novel grading system (well-differentiated [nG1], intermediately [nG2], and poorly differentiated [nG3]) based on a sum score for BA and CNS is highly and independently prognostic for patient survival in LSCC/HSCC, strongly outperforming the current WHO grading scheme with a hazard ratio for disease-specific survival of 6.6 for nG2 and 13.4 for nG3 cases (P<0.001). This finding contributes to a growing body of evidence that a CNS and BA-based pan-entity grading system in SCC might be useful and seems to capture differences in underlying SCC biology crucial for survival.

Diagnostic lymph node extirpation in CUP syndrome - useful or damaging?

OBJECTIVE: In a proportion of patients with cervical lymph node metastasis no primary can be found even with modern imaging and careful clinical examination (cancer of unknown primary syndrome = CUP syndrome). The ideal diagnostic approach is still debated on. METHODS: The clinical data of 75 patients (median age: 61.8 years; 16 females and 59 males), which have been treated for cervical squamous cell carcinoma of unknown primary syndrome in our hospital were retrospectively analyzed. RESULTS: In 12% of patients (n = 9) the primary demarcated in a time period of up to 5.3 years after diagnosis. In the patients who did not receive adjuvant radiotherapy (n = 13), primary became apparent in 38%. Diagnostic lymph node extirpation delayed time until therapeutic neck dissection on average for 3 weeks. In 62% of patients with previous lymph node extirpation (pN2a-N2c), a modified radical neck dissection was required compared to 41% when the surgical site was not operated on. CONCLUSIONS: In 12% of patients' primary demarcated in the course of the disease. A diagnostic lymph node extirpation was compared to direct therapeutic neck dissection after frozen section analysis associated with a three weeks delayed therapy and higher rate of modified radical neck dissection.

Sonographic differentiation between lymphatic and metastatic diseases in cervical lymphadenopathy.

OBJECTIVES/HYPOTHESIS: The spectrum of differential diagnosis in cervical lymphadenopathy is extremely broad. In lymphoma and inflammatory diseases, surgical approaches are restricted to diagnostic lymph extirpation, whereas metastatic outgrowth into regional lymph nodes usually requires neck dissection. Lymph node surgery has to manage the balancing act between sufficient radicality and preservation of functional structures. The current study, therefore, aimed to identify parameters to differentiate between lymph nodes of lymphatic and metastatic origin. STUDY DESIGN: Single-center, retrospective cohort study. METHODS: Clinical and sonographic parameters from all patients who underwent diagnostic cervical lymphadenectomy from 2010 to 2015 (N = 262) were included in this retrospective analysis. Parameters with significant differences between the two subgroups were utilized to create a clinical algorithm to distinguish between cervical lymphadenopathy of lymphatic and metastatic genesis. RESULTS: Statistically significant differences between the two subgroups could be shown for clinical (gender, age, nicotine/alcohol abuse, B symptoms, history of cutaneous melanoma, or lymphoma) and ultrasonographic parameters (string-of-beads confirmation, bilaterality, homogenous echostructure, localization in level I, long-to-short axis ratio, and hilar vascularity). The proposed algorithm yielded a sensitivity of 92.4% for metastatic disease. CONCLUSIONS: The implemented algorithm based on ultrasonographic and clinical criteria contributes to one-step surgical approaches that guarantee a sufficient radicality with a minimum of functional loss. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:859-863, 2018.

Multimodal Ultrasonographic Pathway of Parotid Gland Lesions.

Purpose To evaluate a multimodal pathway in solitary circumscribed parotid gland lesions (PL) to predict tumor dignity and to avoid repeat surgery. Materials and Methods 202 patients with PL underwent medical history, clinical examination, high-resolution B-mode ultrasound (US), real-time sonoelastography (RTE), color-coded duplex sonography (CDS), and contrast-enhanced ultrasound (CEUS). Malignancy was suspected when: 1. patients reported on previous cutaneous head and neck (H&N) malignancy; 2. patients presented synchronous cutaneous H&N malignancy and/or facial palsy; 3. US visualized poorly defined tumor borders and/or pathological cervical lymph nodes; 4. PL showed poor vascularization in CDS with enhanced perfusion kinetics in CEUS; 5. PL showed moderate/strong vascularization with delayed perfusion kinetics. Intraoperative frozen section was performed in PLs suspicious for malignancy, and surgery was extended when malignancy was confirmed. The sensitivity, specificity, negative, and positive predictive values (NPV/PPV) were calculated. Results Histology revealed 170 benign and 32 malignant PLs. Medical history, clinical examination, and B-mode US identified malignancy with a sensitivity/specificity of 77 %/98 %. After application of CDS and CEUS in the multimodal pathway, the sensitivity of malignant tumors increased to 91 %. The decreased specificity (81 %) was equalized by intraoperative frozen section (PPV 48 %, NPV 98 %). After application of the multimodal pathway, only 1 patient underwent repeat surgery. Conclusion The multimodal pathway is a useful method to predict dignity in PLs and reduces the number of repeat surgeries.

Management of locoregional recurrence in cutaneous squamous cell carcinoma of the head and neck.

Cutaneous squamous cell carcinomas often affect elderly patients. Follow-up monitoring is difficult in these patients due to their multi-morbidity and reduced compliance. Tumour recurrence is consequently diagnosed in advanced tumour stages. Surgical therapy with curative intention often requires extended resections. The study at hand should determine whether surgical concepts are warranted in this collective. Sixty-seven patients who underwent surgical procedure due to recurrent disease of cutaneous head and neck squamous cell carcinoma were included. The cohort was divided in patients with/without adjuvant therapeutic regimens. Data were assessed retrospectively. Complete tumour resection was achieved in 85 % of our patients. Patients with adjuvant treatment demonstrated a favorable 5-year-recurrence-free interval (78 vs 30 %) and overall survival (79 vs 46 %). Complete surgical resection of advanced recurrent head and neck cutaneous squamous cell carcinomas is possible and yields favorable results in terms of survival, especially if combined with adjuvant treatment.

Reproducibility of Acoustic Radiation Force Impulse Imaging in Thyroid and Salivary Glands with Experienced and Inexperienced Examiners.

Acoustic radiation force impulse (ARFI) imaging enables the sonographic measurement of tissue stiffness. The aim of this study was to evaluate if experience in ARFI imaging influences the reproducibility of ARFI imaging of the head and neck. Three experienced sonographers and three inexperienced sonographers performed ARFI imaging of thyroid, submandibular and parotid glands in 10 healthy volunteers. The examination was repeated after 2 wk. Ten single ARFI measurements were done in every gland. Inter-rater and intra-rater reliability was analyzed using the intra-class correlation coefficient (ICC). Moderate agreement was observed between experienced and inexperienced examiners (ICC = 0.46). In salivary glands, agreement was fair between the groups (ICC = 0.33), whereas in separate evaluations, inter-rater reliability in the submandibular glands was moderate (ICC = 0.52), and that in the parotid glands, only poor (ICC = 0.09). For ARFI imaging of the thyroid gland, there was moderate agreement between the groups (ICC = 0.50). The intra-rater reliability for the salivary and thyroid glands together and separately was strong in both groups. ARFI imaging of the thyroid and salivary glands did exhibit good reproducibility. ARFI imaging of the thyroid gland reached the highest levels of inter- and intra-observer agreement in both groups. ARFI imaging in salivary glands is only reproducible with experienced examiners.

Effect of liposomal local therapy on salivary glands in acoustic radiation force impulse imaging in Sjögren's syndrome.

The purpose of this study was to evaluate the utility of acoustic radiation force impulse (ARFI) imaging as a monitoring tool for the effect of a liposomal local therapy in patients with dry mouth symptoms due to primary Sjögren's syndrome (pSS). Fifty patients with pSS, diagnosed according to the American-European Consensus Group (AECG) criteria, were included. Clinical data were collected, and sonographic examination including ARFI imaging of the parotid and submandibular glands was performed. Subjective symptoms were evaluated via visual analogue scales (VAS), and the unstimulated whole salivary flow was measured. After a two-month period of liposomal local therapy, sonographic examination was repeated and both subjective and objective symptoms were re-evaluated. Before local treatment, the mean ARFI value of parotid glands was 2.96 m/s (SD 0.97). Mean ARFI value of the submandibular glands was 2.09 m/s (SD 0.71). After the two-month treatment period, a significant decline of ARFI values in the parotid glands to a value of 2.34 m/s (SD 0.70, p < 0.001) could be observed. The submandibular glands did not show any significant change. Further, a significant reduction of the subjective sensation of dry mouth symptoms could be observed (p = 0.0001). With the application of ARFI imaging, a decline in parotid gland stiffness could be observed in patients with primary Sjögren's Syndrome accompanied by a significant improvement of the subjective sensation of dry mouth symptoms. The seromucous submandibular glands did not show any changes compared to the serous parotid glands.

Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency.

Hereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life-threatening. In the majority of cases, the disease can be adequately treated with an on-demand approach--in some cases, however, short- or long-term prophylaxis is indicated. Attenuated androgens used to be the drugs of choice, but they are associated with considerable side effects and no longer commercially available in the German-speaking countries of the EU. They are currently being replaced by more effective and more tolerable agents such C1-inhibitors, the kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant, which have recently obtained market authorization. These new drugs have had a major impact, especially on the indications and procedures for long-term prophylaxis. According to the most recent international consensus papers and our own experience, self-administered C1-inhibitors are now the first option for long-term prophylactic therapy. The decision for prophylaxis should no longer be based on single parameters such as the frequency of attacks but on adequate overall disease control including quality of life. More drugs are currently being developed, which may lead to further changes in the treatment algorithms of HAE.

Nanofiltrated C1-esterase-inhibitor in the prophylactic treatment of bradykinin-mediated angioedema.

BACKGROUND: Patients suffering from bradykinin-induced angioedema show recurrent swelling of subcutaneous and submucosal structures. Increased bradykinin levels lead to an increase in vascular permeability and edema formation. Current therapy consists of B2 bradykinin receptor antagonists, C1-esterase-inhibitor (C1-INH) concentrate, or the kallikrein inhibitor ecallantide. In most cases the treatment of acute attacks is sufficient. Prophylactic therapy is recommended only in severe cases. C1-INHc has been shown a safe and efficient option. Its effect on the quality of life has not yet been analyzed. STUDY DESIGN AND METHODS: Patients with inadequate disease control despite an "on-demand therapy" including C1-INHc and/or the B2 receptor antagonist icatibant were switched to long-term prophylaxis consisting in an individual dose of intravenous C1-INHc (Cinryze). None of the patients had been previously treated with ecallantide. Disease-specific quality-of-life questionnaires and patient records were used for evaluation. Disease control, quality of life, adverse events, and administered dosage per month were compared for 6 months on on-demand therapy and the following 6 months under prophylactic therapy. RESULTS: Data of seven patients with hereditary angioedema (HAE) and one patient with acquired angioedema were evaluated. Prophylactic therapy with Cinryze led to a significant and clinically relevant reduction in the overall attack frequency from 6.7 to 2.3 per month without relevant side effects. The frequency of severe attacks was reduced by 89% and quality of life significantly improved. CONCLUSION: Prophylaxis with Cinryze led to a significantly improved quality of life in our cohort of patients with high-frequency bradykinin-induced angioedema attacks that were not sufficiently treated with on-demand medication.

Bronchogenic cancer: It still exists.

OBJECTIVES/HYPOTHESIS: Branchial cleft cysts rank among the most common differential diagnoses of cystic cervical masses. Rarely, classic cystic structures exhibit a squamous cell carcinoma differentiation that represents a bronchogenic carcinoma. The existence of bronchogenic carcinoma is controversial due to the lack of systematic immunohistologic workup. The present study aimed to identify the clinical and immunohistologic features of bronchogenic carcinoma to clearly distinguish this entity from other cystic cervical masses. METHODS: Immunohistologic (epidermal growth factor receptor; cytokeratin 5, 6, 7, 13; and p16) and epidemiologic assessments were performed for branchial cleft cysts (n = 63), bronchogenic carcinomas (n = 5), cystic metastasized oropharyngeal carcinomas (n = 97), and carcinomas of unknown primary (n = 51). The study was conducted as a retrospective case series study with comparison. RESULTS: The patients with bronchogenic carcinomas differed significantly in age and in the number of involved lymph nodes compared with the cystic metastasized oropharyngeal carcinoma (and carcinoma of unknown primary) patients. Regular histologic wall structures were only observed in the bronchogenic carcinomas and branchial cleft cysts. Solitary cytokeratin-7 staining was only observed in the bronchogenic carcinomas, and all of the bronchogenic carcinomas were p16 negative. CONCLUSIONS: The existence of bronchogenic carcinoma seems to be plausible based on clinical findings. Cytokeratin-7 and p16 staining might be helpful in the diagnostic workflow. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:638-642, 2016.

Orbital complications:diagnosis of different rhinological causes.

To evaluate the clinical course of orbital complication using a standardised diagnostic pathway. Seventy-three patients with orbital complications underwent a multimodal diagnostic pathway comprising ENT examination, leucocytes/CRP, CT-/MRI-scanning and disease-related data. Twenty-nine patients suffered from rhinosinusitis, 28 from mucoceles, 13 patients from neoplasms and three patients from rheumatic disorders. Clinical examination diagnosed 60 patients with eyelid swelling, 55 patients with ocular pain, 14 patients with diplopia, 4 patients with exophthalmus, 29 patients with visual field defect and 4 patients with visual loss. The diagnostic pathway identified acute rhinosinusitis with a sensitivity/specificity of 90 %/90 %, mucoceles with 79 %/100 %, neoplasms with 100 %/96 % and granulomatosis with polyangiitis with 100 %/100 %, respectively. All patients left the hospital in good general condition and with regular ocular motility; two patients suffered persistent visual loss. The standardised application of a widely accepted diagnostic pathway reliably distinguishes different causes of orbital complication.

Survivin and pAkt as potential prognostic markers in squamous cell carcinoma of the head and neck.

OBJECTIVE: The purpose of our study was to investigate the expression patterns of cell cycle regulatory proteins and members of the epidermal growth factor receptor (EGFR) signaling pathway in squamous cell carcinoma of the head and neck (HNSCC). STUDY DESIGN: The expression levels of survivin, Bub1 B (budding uninhibited by benzimidazoles 1 homolog beta), PLK-1 (polo-like kinase 1), Ki-67, cyclin D1, p53, EGFR, pMAPK (phosphorylated mitogen-activated protein kinase), pAkt (phosphorylated protein kinase B), and PTEN (phosphatase and tensin homolog) were studied in a series of 180 tumor samples obtained from HNSCC surgical resections, 50 metastatic lymph node samples, and 72 corresponding noncancerous epithelium samples. Protein expression analysis was performed by immunohistochemical staining. The results were correlated with clinicopathologic features and survival data. RESULTS: Prognostic significance could be found only for the markers survivin and pAkt. Only the marker combination of cyclin D1 and p53 had positive prognosis potential regarding overall survival. CONCLUSIONS: Both pAkt and survivin show a positive correlation with distant metastases and may have utility as predictors of long-term outcomes for patients with HNSCC.

Rheumatic disorders affecting the head and neck: underestimated diseases.

OBJECTIVES: To describe the clinical manifestations of rheumatic disorders with isolated head and neck (H&N) affection and to introduce a novel diagnostic pathway. METHODS: From 2004 to 2010, 90 patients presented with isolated H&N symptoms of a rheumatic disorder were included in the study. Rheumatic disorders were classified according to the ACR criteria. In 2008, we introduced a novel diagnostic pathway to reduce under-diagnosis of primary rheumatic disorders in the H&N. Disease-related data were assessed retrospectively and set into clinical context. RESULTS: The majority of patients suffered from SS (n = 42), granulomatosis with polyangiitis (Wegener's) (n = 13) and sarcoidosis (n = 18) with predominance for female patients (n = 65). Enlargement of the major salivary glands (n = 47), sicca symptoms (n = 41) and cervical lymphadenopathy (n = 25) represented the most frequent symptoms. Interestingly, 3% of all enlargements of salivary glands and 4% of all cervical lymphadenopathy could be contributed to rheumatic disorders. The mean time to diagnosis was 20.71 months for SS, 8.4 months for granulomatosis with polyangiitis and 57.5 months for sarcoidosis. After implementation of the newly developed diagnostic pathway in 2008, the annually diagnosed rheumatic disorders increased 5-fold. CONCLUSIONS: The majority of rheumatic diseases of the H&N can be related to SS, granulomatosis with polyangiitis and sarcoidosis. However, the lack of specific symptoms and the clinical variability of H&N manifestation may contribute to a prolonged time to diagnosis. Our retrospective study points out the variability of symptoms and suggests a diagnostic pathway to reduce the cases of undetected H&N affection in rheumatic disorders.