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(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.

Despite modern therapies with tyrosine kinase inhibitors (TKI), the management of patients with metastatic renal cell carcinoma (mRCC) remains a challenge. Significant immunosuppression has been described in patients with mRCC. Therefore, immunotherapeutic strategies such as checkpoint inhibitors have been developed. To further elucidate the underlying mechanisms of immunosuppression and response by therapy, different features of the immune microenvironment (expression of HIF-1-{alpha}, VEGFR-1, FOXP3, TGF-{beta}1, CD80, CD86, PD-1, and PD-L1) were analyzed in tumor tissues within different subgroups of mRCC patients (responders vs. non-responders to therapy). Results: The most interesting finding was low level CD80 and CD86-expression on tumor tissue samples (n = 18) of nearly all mRCC patients. This finding was in line with CD86 expression, which could also be found in renal carcinoma cell lines. To the best of our knowledge, this is the first report on CD820/CD86 expression in human renal cell carcinoma-possibility reflecting an immunomodulatory mechanism of the tumor.

Introduction/ Background More than six years ago – accompanying the start of the new study program “Modellstudiengang” – we began a virtual microscopy program for our students. This started with slides to accompany the course to use during the lesson and for review of the slides at home (or in the library). But we wanted to go further. How far have we come? Aims Our aim was to provide our students with more benefi- cial information and to increase the amount of material available - in the form of slides and accompanying exercises. A secondary goal was streamlining the education of our students (fewer slides to manage and better opportuni- ties for students to prepare for lessons). Methods The slides were scanned using NanoZoomer 2.0-HT slide scanner. The virtual slides were made available to students using Slidebox system (version 4.4.3.) in three different ways:We provided annotated slides with healthy (physio- logical) and diseased (pathological) samples to ac- company the entire course. Some of the slides were for use during lessons, others as supplementary material. • The virtual slides were integrated into a new style of lecture (“blended learning”) mixing learning opportu- nities from case reports, including clinical information; radiological images; and virtual slides. To review acquired knowledge memory-quizzes were used. • We complement the cases seen in the practical course “Autopsy – How, why, to what end?” with histology. Thus students are able to have a complete overview of the case from clinical history, to macroscopic findings and their correlation with the microscopic findings, to the final report. Results Usually the students were suprised, when they first come in contact with the virtual microscopy. But the Initial suprise yields to experimentation and getting used to it. Virtual microscopy is not only just a part, but an import- ant part of our education., Diagnostic Pathology, Vol 1 No 8 (2016): 13. European Congress on Digital Pathology

Einleitung: In unserer Fallvorstellung handelt es sich um einen Biss eines Tylosurus crocodilus, der in den Tropen und Subtropen beheimatet ist. Unfälle durch diese Fischart beim Menschen sind in der Literatur beschrieben und werden meist durch die scharfen Zähne beim plötzlichen Herausspringen des Fisches aus dem Wasser verursacht. Fallvorstellung: In unserer Klinik sahen wir im März 2015 einen 36-jährigen Patienten, der drei Wochen zuvor beim Baden in Thailand, einen Fischbiss eines Tylosurus Crocodilus in das linke Ohr erlitt. Der Patient klagte über anhaltende starke Ohrenschmerzen links und Beschwerden beim Kauen. Im HNO-Spiegelbefund zeigte sich ein knöcherner Defekt des Gehörgangsdaches links sowie ein Fistelmaul oberhalb des Tragus. In der Computertomographie des Felsenbeines war ein knochendichter 42 mm langer Fremdkörper, der von oberhalb des Tragus entlang des Gehörganges und durch das linke Kiefergelenk bis nach parapharyngeal zieht, zu verzeichnen. Wir führten eine Fremdkörperexstirpation in ITN durch. Intraoperativ zeigte sich ein mehrfach frakturierter Fremdkörper, der unter mikroskopischer Sicht schrittweise geborgen wurde. Histologisch ergab sich ein avitaler Knochen untypischer Morphologie für humanes Gewebe sowie eine chronische Entzündung im angrenzenden fibrosierten Weichgewebe. Zur näheren Begutachtung des Fischpräparates wurde zusätzlich das Naturkundemuseum von Berlin involviert. Zusammenfassung: Fischfremdkörper des Tylosurus crocodilus können durch die scharfen, nadelartigen Zähne des Fischmaules ein kompliziertes Verletzungsmuster der Otobasis und des benachbarten Kiefergelenkes verursachen. Der Erstautor gibt keinen Interessenkonflikt an., GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 12:Doc042

INTRODUCTION / BACKGROUND: More than six years ago – accompanying the start of the new study program “Modellstudiengang” – we began a virtual microscopy program for our students. This started with slides to accompany the course to use during the lesson and for review of the slides at home (or in the library). But we wanted to go further. How far have we come? AIMS: Our aim was to provide our students with more benefi- cial information and to increase the amount of material available - in the form of slides and accompanying exercises. A secondary goal was streamlining the education of our students (fewer slides to manage and better opportuni- ties for students to prepare for lessons). METHODS: The slides were scanned using NanoZoomer 2.0-HT slide scanner. The virtual slides were made available to students using Slidebox system (version 4.4.3.) in three different ways:We provided annotated slides with healthy (physio- logical) and diseased (pathological) samples to ac- company the entire course. Some of the slides were for use during lessons, others as supplementary material. The virtual slides were integrated into a new style of lecture (“blended learning”) mixing learning opportu- nities from case reports, including clinical information; radiological images; and virtual slides. To review acquired knowledge memory-quizzes were used. We complement the cases seen in the practical course “Autopsy – How, why, to what end?” with histology. Thus students are able to have a complete overview of the case from clinical history, to macroscopic findings and their correlation with the microscopic findings, to the final report. RESULTS: Usually the students were suprised, when they first come in contact with the virtual microscopy. But the Initial suprise yields to experimentation and getting used to it. Virtual microscopy is not only just a part, but an import- ant part of our education.

Background Despite clear differences in clinical presentation and outcome, squamous cell carcinomas of the head and neck (SCCHN) arising from human papilloma virus (HPV) infection or heavy tobacco/alcohol consumption are treated equally. Next-generation sequencing is expected to reveal novel targets for more individualised treatment. Patients and methods Tumour specimens from 208 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity, all uniformly treated with adjuvant cisplatin-based chemoradiation, were included. A customised panel covering 211 exons from 45 genes frequently altered in SCCHN was used for detection of non-synonymous point and frameshift mutations. Mutations were correlated with HPV status and treatment outcome. Results Mutational profiles and HPV status were successfully established for 179 cases. HPV– tumours showed an increased frequency of alterations in tumour suppressor genes compared to HPV+ cases (TP53 67% versus 4%, CDKN2A 18% versus 0%). Conversely, HPV+ carcinomas were enriched for activating mutations in driver genes compared to HPV– cases (PIK3CA 30% versus 12%, KRAS 6% versus 1%, and NRAS 4% versus 0%). Hotspot TP53 missense mutations in HPV– carcinomas correlated with an increased risk of locoregional recurrence (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.5–12.1, P = 0.006) and death (HR 2.2, 95% CI 1.1–4.4, P = 0.021). In HPV+ SCCHN, driver gene mutations were associated per trend with a higher risk of death (HR 3.9, 95% CI 0.7–21.1, P = 0.11). Conclusions Distinct mutation profiles in HPV– and HPV+ SCCHN identify subgroups with poor outcome after adjuvant chemoradiation. Mutant p53 and the phosphoinositide 3-kinase pathway were identified as potential druggable targets for subgroup-specific treatment optimisation.

Einleitung: Bislang konnte bei Kopf-Hals-Karzinomen kein Biomarker zum Screening oder zur Verlaufsbeurteilung etabliert werden. In dieser Studie untersuchten wir den bereits bei colorectalen Malignomen, malignen Gliomen, Blasenkarzinom, Brustkrebs und Endometriumkarzinom bekannten RHAMM Rezeptor in Kopf- Hals Karzinomen. Da der RHAMM Rezeptor eng mit der Migrationsfähigkeit des Tumors korreliert, müsste eine Aussage zur Metastasierungswahrscheinlichkeit gemacht werden können. Methoden: 60 Patienten unserer Nachsorgesprechstunde haben wir nach der Tumorlokalisation (Orophaynx, Hypopharynx und Larynx) getrennt beurteilt. Anamnese, Ausdehnung des Primärtumors und Metastasen-Status wurden mit Vorhandensein von CD168 im histologischen Schnitt des Tumors bei Erstdiagnose verglichen. Ergebnisse: In den ersten Ergebnissen konnten wir keine Korrelation feststellen. Allerdings wurde hierbei das Vorhandensein des extrakapsulären Wachstums der cervikalen Lymphknotenmetastasen nicht mit in die Untersuchung einbezogen. Schlussfolgerungen: Auf dem ersten Blick scheint die Expression von CD168 nicht mit der Tumorausdehnung und dem Metastasierungsverhalten zu korrelieren. Weitere detailiertere Untersuchungen sind nötig um eine mögliche Anwendung von CD168 als Biomarker zu evaluieren. Der Erstautor gibt keinen Interessenkonflikt an., GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 11:Doc325; ISSN 1865-1038

Primäre Lymphome des zentralen Nervensystems, stellen etwa 1–3% aller primären Hirntumore dar. Eine Neurolymphomatose des peripheren Nervensystems durch Infiltration von Lymphomen ist eine Seltenheit. Wenn eine Beteiligung vorliegt ist diese in der Regel sekundär bedingt. Bislang wurde von sehr wenigen Fällen einer Erstmanifestation eines B-Zell Lymphoms im peripheren Nervensystem berichtet. In den meisten Fällen jedoch zeigt sich eine zeitgleiche Beteiligung des zentralen Nervensystems mit positiver Liquor Analyse, leptomeningealer Beteiligung, Infiltration von Nervenwurzeln, den Plexus oder der Hirnnerven. Dies könnte darauf hindeuten, dass in diesen Fällen die Infiltration des peripheren Nervensystems sekundär bei primärer Manifestation des zentralen Nervensystems erfolgte. Wir berichten über einen 57-jährigen Patienten, welcher sich mit einer asymptomatischen Lymphadenitis colli links, als Zufallsbefund, ohne nervale Ausfälle oder B-Symptome vorstellte. Bildmorphologisch zeigte sich im MRT des Halses eine langstreckige, glattbegrenzte atypisch enhancende Raumforderung links zervikal. Eine anatomische Zuordnung war hierdurch, als auch sonographisch nicht möglich. Intraoperativ zeigte sich an den aus dem Erb’schen Punkt entspringenden sensiblen Nerven eine ummantelnde weiche und helle Raumforderung Nach histologischer und immunhistochemischer Aufarbeitung der Biopsie des N. transversus zeigte sich ein CD-30 exprimierendes diffus großzelliges B-Zell-Lymphom. Der Patient wurde in der Klinik für Onkologie mit einer Chemotherapie nach dem R-CHOP Schema behandelt. In der aktuellen Literatur liegen nach unseren Recherchen bisher keine Fallbeschreibungen eines isolierten Befalls eines peripheren, sensiblen Nervens vor. Der Erstautor gibt keinen Interessenkonflikt an., GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 10:Doc180; ISSN 1865-1038

Antibodies against PD-1 and PD-L1 can cause strong and durable anti-tumor immune responses in non-small cell lung cancer (NSCLC). Immunohistochemistry for PD-L1 (PD-L1 IHC) was tested as a predictive biomarker. Several IHC assays and interpretation criteria were developed in parallel.The clinical significance of PD-L1 IHC in NSCLC and the optimum method for staining and interpretation of the results are the subject of ongoing studies. The diagnostic application of immunotherapy in NSCLC necessitates harmonization of PD-L1 IHC to obtain evidence for guidelines; therefore, a consensus opinion on a well-founded diagnostic mode of testing should be defined based on published studies and the results of the first German PD-L1 IHC harmonization study.1. Summary of the current data situation. 2. Evaluation of the first German PD-L1 IHC harmonization study (centralized, staining with PD-L1 IHC analogous to studies, 15 cases of NSCLC, 4 IHC study assays [28‑8, 22C3, SP142 and SP263] and scoring by 9 pathologists).The use of PD-L1 IHC in NSCLC is suitable for identification of patients with an increased probability of a clinical benefit from immunotherapy. The various proportional cut-offs used to interpret the staining results can be summarized in a total score, which can be reproducibly assessed. The staining patterns of the four assays investigated were, however, not congruent in all situations.In principle, the use of PD-L1 IHC for assessment of the expression in tumor cells is a reliably determinable biomarker. Evaluation algorithms should be based on published clinical trials. For NSCLC approvals with obligatory PD-L1 IHC are to be expected but it remains to be seen to what extent PD-L1 IHC will be implemented in the clinical routine.