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As lung cancer has the highest cancer-specific mortality rates worldwide, there is an urgent need for new therapeutic and diagnostic approaches to detect early-stage tumors and to monitor their response to the therapy. In addition to the well-established tissue biopsy analysis, liquid-biopsy-based assays may evolve as an important diagnostic tool. The analysis of circulating tumor DNA (ctDNA) is the most established method, followed by other methods such as the analysis of circulating tumor cells (CTCs), microRNAs (miRNAs), and extracellular vesicles (EVs). Both PCR- and NGS-based assays are used for the mutational assessment of lung cancer, including the most frequent driver mutations. However, ctDNA analysis might also play a role in monitoring the efficacy of immunotherapy and its recent accomplishments in the landscape of state-of-the-art lung cancer therapy. Despite the promising aspects of liquid-biopsy-based assays, there are some limitations regarding their sensitivity (risk of false-negative results) and specificity (interpretation of false-positive results). Hence, further studies are needed to evaluate the usefulness of liquid biopsies for lung cancer. Liquid-biopsy-based assays might be integrated into the diagnostic guidelines for lung cancer as a tool to complement conventional tissue sampling.

Via immunohistochemistry (IHC) on tissue micro arrays (TMA) clinical and prognostic impact of p53 co-playing 5′-Nucleotidase Domain-Containing Protein 2 (NT5DC2) protein expression was evaluated in 252 NSCLC patients. Confirmatory, gene expression database. mRNA levels of NT5DC2 were studied in 1925 NSCLC patients. High protein expression of NT5DC2 resulted in reduced median overall survival (OS) of patients with stage I-III adenocarcinoma (ADC) (Log Rank p = 0.026, HR 2.04 (1.08–3.87)), but not in squamous cell carcinoma (SCC) (p = 0.514, HR 0.87 (0.57–1.33)). Findings on OS were reproduced via gene expression analysis in ADC (p < 0.001, HR 1.64 (1.30–2.08)) and SCC (p = 0.217, HR 0.86 (0.68–1.09)). Yet, NT5DC2 mRNA levels were higher in SCC compared to ADC (p < 0.001) and in pN2 tumors compared to pN0/1 tumors (p = 0.001). Likewise, NT5DC2 protein expression associated with high-grade SCC. Moreover, NT5DC2 expression was positively correlated with p53 protein (p = 0.018) and TP53 gene expression (p < 0.001) and its survival effect was p53 dependent. While p53 expression was negatively associated with the presence of CD34+ cancer associated fibroblasts (CAFs), NT5DC2 expression insignificantly tended to higher levels of SMA+ CAFs (p = 0.065).

BACKGROUND: T cell infiltration in non-small cell lung cancer (NSCLC) is essential for the immunological response to malignant tissue, especially in the era of immune-checkpoint inhibition. To investigate the prognostic impact of CD4(+) T helper cells (T(h)), CD8(+) cytotoxic (T(c)) and FOXP3(+) regulatory T (T(reg)) cells in NSCLC, we performed this analysis. METHODS: By counterstaining of CD4, CD8 and FOXP3 we used immunohistochemistry on tissue microarrays (TMA) to evaluate peritumoral T(h) cells, T(reg) cells and T(c) cells in n=294 NSCLC patients with pTNM stage I–III disease. RESULTS: Strong CD4(+) infiltration was associated with higher tumor stages and lymphonodal spread. However, strong CD4(+) infiltration yielded improved overall survival (OS) (P=0.014) in adenocarcinoma (ADC) and large cell carcinoma (LCC) but not in squamous cell carcinoma (SCC). A CD4/CD8 ratio 0.05). Here, prognostic effects were prominent in PD-L1 positive SCC (P=0.023) but not in PD-L1 negative SCC (P=0.236). CONCLUSIONS: High proportion of CD8(+) T(c) cells correlated with improved prognostic outcome in stage I–III NSCLC. T(h) cells and T(reg) cells have implications on outcome with respect to tumor histology and biology.

Background. Following COVID-19, patients often present with ongoing symptoms comparable to chronic fatigue and subjective deterioration of exercise capacity (EC), which has been recently described as postacute COVID-19 syndrome. Objective. To objectify the reduced EC after COVID-19 and to evaluate for pathologic limitations. Methods. Thirty patients with subjective limitation of EC performed cardiopulmonary exercise testing (CPET). If objectively limited in EC or deteriorated in oxygen pulse, we offered cardiac stress magnetic resonance imaging (MRI) and a follow-up CPET. Results. Eighteen male and 12 female patients were included. Limited relative EC was detected in 11/30 (36.7%) patients. Limitation correlated with reduced body weight-indexed peak oxygen (O2) uptake (peakV̇O2/kg) (mean 74.7 (±7.1) % vs. 103.6 (±14.9) %, p < 0.001 ). Reduced peakV̇O2/kg was found in 18/30 (60.0%) patients with limited EC. Patients with reduced EC widely presented an impaired maximum O2 pulse (75.7% (±5.6) vs. 106.8% (±13.9), p < 0.001 ). Abnormal gas exchange was absent in all limited EC patients. Moreover, no patient showed signs of reduced pulmonary perfusion. Using cardiac MRI, diminished biventricular ejection fraction was ruled out in 16 patients as a possible cause for reduced O2 pulse. Despite noncontrolled training exercises, follow-up CPET did not reveal any exercise improvements. Conclusions. Deterioration of EC was not associated with ventilatory or pulmonary vascular limitation. Exercise limitation was related to both reduced O2 pulse and peakV̇O2/kg, which, however, did not correlate with the initial severity of COVID-19. We hypothesize that impaired microcirculation or limited peripheral O2 utilization might be causative for prolonged deterioration of EC following acute COVID-19 infection.

Treatment of advanced stage anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) with ALK tyrosine kinase inhibitors (TKIs) has been shown to be superior to standard platinum-based chemotherapy. However, secondary progress of disease frequently occurs under ALK inhibitor treatment. The clinical impact of re-biopsies for treatment decisions beyond secondary progress is, however, still under debate. Here, we report on two novel subsequent polyclonal on-and off-target resistance mutations in a patient with ALK-fused NSCLC under ALK inhibitor treatment. A 63-year-old male patient with an advanced stage EML4-ALK fused pulmonary adenocarcinoma was initially successfully treated with the second-generation ALK inhibitor alectinib and upon progressions subsequently with brigatinib, lorlatinib and chemoimmunotherapy (CIT). Progress to alectinib was associated with a so far undescribed ALK mutation (p.A1200_G1201delinsW) which was, however, tractable by brigatinib. An off-target KRAS-mutation (p.Q61K) occurred in association with subsequent progression under second-line TKI treatment. Third-line lorlatinib showed limited efficacy but chemoimmunotherapy resulted in disappearance of the KRAS mutant clone and clinical tumor control for another eight months. In conclusion, we suggest molecular profiling of progressive tumor disease also for ALK-positive NSCLC to personalize treatment in a subgroup of ALK-positive patients. CA extern

Objectives/hypothesis Recurrent respiratory papillomatosis (RRP) is a primarily benign disease affecting the entire respiratory tract. Treatment is challenging and usually involves surgical interventions and adjuvant medications. Previously, promising results on systemic administration of bevacizumab have been reported. However, experience on long-term systemic use in patients with RRP is not yet available. Here, we present our long-term follow-up on RRP patients undergoing systemic bevacizumab treatment. Study design Case series. Methods To describe experience on long-term systemic bevacizumab administration, we performed the underlying investigation. Clinical, radiological, and bronchoscopy data were collected. Results To date, a total of n = 5 patients has been treated with systemic bevacizumab at Muenster University Hospital. With a median follow-up since first systemic bevacizumab administration of 95.5 months long-term follow-up is illustrated. Following bevacizumab treatment partial remission or very good partial remission were achieved in all patients. After papilloma recurrence/progression due to bevacizumab discontinuation, further response was documented in all patients in whom bevacizumab was started again. In one patient, bevacizumab was discontinued due to loss of efficacy. Lung cancer developed in one patient with pulmonary papillomatosis prior to bevacizumab administration whereas three patients suffered from malignant transformation during bevacizumab treatment. Systemic bevacizumab led to long-term reduction in surgical interventions in all patients. Except from mild proteinuria and hypertension in two patients therapy was well tolerated. Conclusions Systemic bevacizumab represents a promising long-term treatment option for aggressive forms of papillomatosis. Rate of malignant transformation under bevacizumab treatment, optimal treatment schedule, and influence on survival should be further evaluated in clinical trials. Level of evidence 4 Laryngoscope, 131:E1926-E1933, 2021.

Lack of sensitive diagnostic tests impairs the understanding of the epidemiology of histoplasmosis, a disease whose burden is estimated to be largely underrated. Broad-range PCRs have been applied to identify fungal agents from pathology blocks, but sensitivity is variable. In this study, we compared the results of a specific Histoplasma qPCR (H. qPCR) with the results of a broad-range qPCR (28S qPCR) on formalin-fixed, paraffin-embedded (FFPE) tissue specimens from patients with proven fungal infections (n = 67), histologically suggestive of histoplasmosis (n = 36) and other mycoses (n = 31). The clinical sensitivity for histoplasmosis of the H. qPCR and the 28S qPCR was 94% and 48.5%, respectively. Samples suggestive for other fungal infections were negative with the H. qPCR. The 28S qPCR did not amplify DNA of Histoplasma in FFPE in these samples, but could amplify DNA of Emergomyces (n = 1) and Paracoccidioides (n = 2) in three samples suggestive for histoplasmosis but negative in the H. qPCR. In conclusion, amplification of Histoplasma DNA from FFPE samples is more sensitive with the H. qPCR than with the 28S qPCR. However, the 28S qPCR identified DNA of other fungi in H. qPCR-negative samples presenting like histoplasmosis, suggesting that the combination of both assays may improve the diagnosis.

Background. Alpha-1 antitrypsin deficiency (AATD) is of importance in the pathogenesis of pulmonary emphysema, chronic obstructive pulmonary diseases (COPD), and bronchiectasis. Various pulmonary disorders are a typical feature of primary immunodeficiency disease (PID). This includes recurrent pulmonary infections, immunodysregulation, and autoinflammatory diseases. As a result, incidence of acute and chronic pulmonary diseases is higher. Interestingly, pulmonary morbidity in PID and AATD share similar features. To study the coexistence of AATD in patients suffering from PID, we performed the underlying investigation. Methods. We evaluated a study group of 149 patients (n = 149) with PID. In total, serum AAT concentrations were available for 110 patients (n = 110). For the identified patients, we analyzed both clinical associations and interactions. Results. Among the investigated patients, reduced serum AAT levels were detected in 7 patients. With regard to the genotype, PI∗ZZ was found in 2 patients, whereas PI∗MZ was observed in 5 patients. Independent of the underlying phenotype, obstructive lung diseases were found in 2 patients with PI∗ZZ and 2 patients with PI∗MZ. Conclusions. In Germany, the estimated percentage for PI∗ZZ and PI∗MZ is 0.01% and 1.9%, respectively. As demonstrated, the ratio in our study group was even higher. We identified seven patients with AATD. Since AATD contributes to pulmonary morbidity in PID patients, systematic underdiagnosis of the coexistence might yield a strong clinical impact. Hence, AAT analysis should be offered to all patients with confirmed PID diagnoses. To strengthen this finding, we suggest the investigation of larger databases.

BACKGROUND Follicular lymphoma (FL) is the most frequent indolent lymphoma subtype in adults. Maintenance therapy with rituximab is frequently applied to FL patients with complete or partial response following initial chemoimmunotherapy. However, radioimmunotherapy with 90 Y-ibritumomab-tiuxetan represents a therapeutic alternative. METHODS To compare the clinical and the prognostic impact of both therapies, a study collective of n = 56 patients diagnosed with indolent B-cell lymphoma was retrospectively investigated. The study collective was subdivided into two groups: n = 36 patients treated with rituximab maintenance therapy vs n = 20 patients treated with 90 Y-ibritumomab-tiuxetan. RESULTS No prognostic differences for performance status, FLIPI score, gender, or B-symptoms were found for 90 Y-ibritumomab-tiuxetan or rituximab maintenance therapy. Overall survival rates and progression-free survival did not differ between both maintenance therapies. CONCLUSION Our retrospective single-center analysis of two patient groups without major differences in prognostic parameters revealed similar outcome with two different maintenance therapies. Hence, 90 Y-ibritumomab-tiuxetan therapy might offer a valuable alternative treatment option for FL patients with partial response. However, large prospective trials are needed to confirm the reported findings.

Background: Severe pulmonary hemorrhage is a life-threatening complication in critically ill patients. Due to tracheobronchial obstruction, ventilation is often impaired. Traditionally, rigid bronchoscopy is an option for recanalization. However, in comparison to flexible bronchoscopy, the application of rigid bronchoscopy is more complex. Against this background we evaluated the use of flexible cryo-probes for blood clot removal in critically ill patients. Methods: Retrospectively, we identified 16 patients (median age: 60 years, 69% male patients), who suffered from severe airway obstruction due to blood clots. All patients required invasive ventilation and 11 patients depended on extracorporeal membrane oxygenation (ECMO). To remove blood clots, flexible bronchoscopic cryoextraction was performed in n=27 cases, whereas rigid bronchoscopy was only needed in two cases. Results: Whereas in 9 cases single flexible cryoextraction was successful immediately, the procedure had to be repeated again in 7 patients. In all cases, tracheobronchial obstruction was treated with success and conditions of invasive ventilation were improved. In no case severe complications were observed. Conclusions: In consideration of the underlying evaluation, we highly recommend flexible cryoextraction as both a safe and less complex technique for blood clot removal in critically ill patients.

OBJECTIVES The influence of blood group antigens on cancerogenesis is shown for distinct tumor types, yet the impact of Rhesus blood group antigens in lung cancer is not clarified. MATERIALS AND METHODS To investigate the impact of Rhesus blood groups a non-small cell lung cancer (NSCLC) collective (n = 1047) was analyzed retrospectively. Using a second cohort of n = 340 primarily operated stage I-III NSCLC patients, we evaluated immunohistochemistry of CD47-antibody stained tissue samples in correlation to histopathologic subtype and Rhesus blood group. RESULTS AND CONCLUSION In 516 of 1047 patients blood group data were available. Seven different RhCE phenotypes were grouped as "··ee," "ccE·," and "C·E·." Adenocarcinoma patients with Rh "··ee" revealed improved overall survival (29 (21.2-36.8) m; HR 1.00 [index]) compared with Rh "ccE·" (19 (1.9-36.1) m; HR 1.76 [1.15-2.70]) and Rh "C·E·" (10 (7.4-12.6) m; HR 2.65 [1.70-4.12]) univariately (P

Background Epithelial‐to‐mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer‐associated fibroblasts (CAFs) are reported to regulate this process. Objectives To investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non‐small cell lung cancer (NSCLC). Methods Retrospectively, immunohistochemistry was performed to study stromal protein expression of both CD34 and SMA in 304 NSCLC patients with pTNM stage I‐III disease. All tissue samples were embedded on tissue microarrays (TMAs). Results Our analysis revealed an association for CD34+ CAFs with G1/2 tumors and adenocarcinoma histology. Moreover CD34+ CAFs were identified as an independent prognostic factor (both for progression free survival [PFS] and overall survival [OS] in stage I‐III NSCLC). Besides, SMA+ expression correlated with higher pTNM‐tumor stages and lymphatic spread (pN stage). In turn, SMA‐negativity was associated with improved PFS, but no prognostic impact was found on OS. Of interest, neither CD34+ CAFs nor SMA+ CAFs were associated with the primary tumor size, localization and depth of infiltration (pT stage). Conclusions CD34 was identified as an independent prognostic marker in pTNM stage I‐III NSCLC. Moreover, loss of CD34+ CAFs might influence the dedifferentiation of the NSCLC tumor from its cell origin. Finally, SMA+ CAFs are more prevalent in NSCLC tumors of higher stages and lymphonodal positive NSCLC. Key points Expression of CD34 on cancer associated fibroblasts (CAFs) is an independent prognostic factor in stage I‐III NSCLC.SMA+ cancer associated fibroblasts are associated with higher tumor stages in NSCLC and might contribute to tumor progression in NSCLC.

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkpoint inhibition yielded improved overall survival. Although there are promising molecular pathways with potential therapeutic impacts, targeted therapies are still not an integral part of routine treatment. Against this background, we evaluated current literature for potential new molecular candidates such as surface markers (e.g., DLL3, TROP-2 or CD56), apoptotic factors (e.g., BCL-2, BET), genetic alterations (e.g., CREBBP, NOTCH or PTEN) or vascular markers (e.g., VEGF, FGFR1 or CD13). Apart from these factors, the application of so-called ‘poly-(ADP)-ribose polymerases’ (PARP) inhibitors can influence tumor repair mechanisms and thus offer new perspectives for future treatment. Another promising therapeutic concept is the inhibition of ‘enhancer of zeste homolog 2’ (EZH2) in the loss of function of tumor suppressors or amplification of (proto-) oncogenes. Considering the poor prognosis of SCLC patients, new molecular pathways require further investigation to augment our therapeutic armamentarium in the future.

The better understanding of interactions between tumor and immune system (e.g., tumor-associated upregulation of PD-L1 to induce checkpoint for cytotoxic lymphocytes; Figure 1A ) gave rise to the development of immune modulating therapies.

Background: The cancer registry Northrhine-Westphalia (CR NRW) is state-law based, prospective cancer registry, including all state residents with the diagnosis of cancer (NRW counts approx. 18 million residents). Methods: All MM cases diagnosed and collected between 2010 and 2012 in CR NRW were included (n=1199). 232 cases contained incomplete datasets. In 755 of 967 valid cases (78.1%) the original pathology report was visible, in 468 cases (48.4%) including immunohistochemistry. Results: Of 967 patients with MM 796 were male (82.3%) and 171 female (17.7%), 81.8% were already diseased upon last validation date. Based on ICD-codes 885 patients (91.5%) suffered from pleural MM (C45.0), 72 (7.4%) had peritoneal MM, 2 (0.2%) pericardial MM and 8 (0.8%) had various MM locations. Histology showed predominantly epithelioid growing pattern (60.4%), followed by biphasic growth (13.4%) and sarcomatoid growth (9.4%); in 16.8% the growing pattern was not defined. Median overall survival (OS) of pleural MM was 12.4 months (95%KI 11.3-13.4; all histologies), OS of peritoneal MM was 15.1 months (95%KI 4.5-25.7; all histologies). Multivariate analysis revealed gender, age, histological subtype, cell specific growing features (spindle cell type; papillary type), necrosis, hyaline plaques and proliferation marker Ki67 as independent prognostic factors (p Conclusion: The comprehensive, state-law embedded cancer registry NRW ensures the complete area-wide identification and collection of cancer patients’ course out of 18 million residents. In this very large study MM cell specific growing features and proliferation index could be identified as new independent markers of MM outcome.

Introduction: Alpha-1 antitrypsin deficiency (AATD) plays an important role in the pathogenesis of both emphysema and chronic obstructive pulmonary diseases (COPD). Chronic pulmonary morbidity is also a typical feature of primary immunodeficiency disease (PID) comprising a large spectrum of heterogeneous disorders mostly accompanied by hypogammaglobulinemia and recurrent pulmonary infections. Since we had identified one patient with AATD we decided to screen a larger number of PID patients. Material and Methods: Against this background we evaluated n = 142 cases diagnosed with PID in our institution according to the current ESID criteria. Serum AAT concentration was available for n = 100 patients. Clinical associations and interactions were evaluated. Results: Among the investigated patients, reduced serum AAT levels were detected in n = 7 patients. With regard to the phenotype, PI*ZZ was found in n = 2 patients, whereas PI*MZ was observed in n = 5 patients. Independent from the underlying phenotype, obstructive lung disease was found in n = 2 patients with PI*ZZ and n = 2 patients with PI*MZ. Discussion: In Germany, estimated percentage for PI*ZZ and PI*MZ is 0.01% and 1.9%, respectively. In contrast, the ratio in our study collective of 100 patients was higher, since we identified seven patients with AATD. Since AATD contributes to pulmonary morbidity in PID patients, systematic underdiagnosis of the coexistence might yield a strong clinical impact. To address this issue, AAT analysis should be offered to all patients with confirmed PID diagnosis. Without doubt, larger database analysis is required to confirm our retrospective observations.

Besides invasive or non-invasive ventilation, treatment of severe forms of interstitial lung diseases (ILD) includes immunosuppressive medication. In case of refractory organ- or life-threatening courses of disease, cyclophosphamide pulse therapy can serve as a rescue treatment option.To investigate therapeutic and prognostic effects of cyclophosphamide for the treatment of severe forms of ILD on intensive care unit (ICU) we performed this analysis.Between 2009 and 2017 we identified 14 patients, who were treated on intensive care unit (ICU) with severe forms of ILD. Retrospectively, clinical, radiologic and prognostic data were collected and evaluated.Our analysis demonstrated a prognostic impact of cyclophosphamide on the ILD in general. Whereas pulmonary manifestations of both systemic sclerosis (SSc) and ANCA-associated vasculitis had an improved outcome, a reduced overall survival was found for Goodpasture syndrome (GPS), dermatomyositis (DM), cryptogenic organizing pneumonia (COP) and drug reaction with eosinophilia and systemic symptoms (DRESS; p=0.040, logrank test). Besides, additional plasmapheresis and initiation of cyclophosphamide within ten days following initial diagnosis of ILD were associated with improved prognosis.Positive prognostic effects of cyclophosphamide pulse therapy in ICU treated patients suffering from severe respiratory failure due to pulmonary manifestations of both SSc and ANCA-associated-vasculitis were observed. Further prognostic and therapeutic data are needed for cyclophosphamide for this indication in order to prevent patients from its toxic side-effects, who most likely will not benefit from its application.

Nivolumab in a patient with refractory Hodgkin’s lymphoma after allogeneic stem cell transplantation

Histoplasmosis in central Europe is a rare fungal disease with diverse clinical presentations. Apart from acute pulmonary histoplasmosis and involvement of the central nervous system, the most serious clinical presentation is progressive disseminated histoplasmosis which is generally associated with severe immunodeficiency and, in particular, advanced human immunodeficiency virus infection. Here, we report on an immunocompetent female residing in a non-endemic area, presenting with progressive disseminated histoplasmosis after a remote travel history to Thailand and Costa Rica. Diagnosis was delayed by several months due to misinterpretation of epithelioid cell granulomatosis of the intestine as Crohn's disease and of similar lung lesions as acute sarcoidosis. Prompted by clinical deterioration with signs and symptoms consistent with hemophagocytic lymphohistiocytosis, a bone marrow aspiration was performed that documented hemophagocytosis and intracellular organisms interpreted as Leishmania sp., but later identified by molecular methods as Histoplasma capsulatum. Treatment with liposomal amphotericin B followed by posaconazole led to prompt clinical improvement and ultimately cure.

Objectives In patients with testicular Germ Cell Tumors (GCT) noncaseating granulomatous diseases such as Sarcoid Like Lesions (SLL) or Sarcoidosis can mimic metastasis due to hilar or mediastinal lymphadenopathy. Due to the clinical and prognostic impact, exclusion of malignant diseases is mandatory. Material and methods Retrospectively, data from 636 GCT patients, who were seen in the course of tumor surveillance/follow-up were collected. Focus was put on the detection of tumor relapse vs. noncaseating granulomatous reactions. For the differential diagnosis of thoracic lymphadenopathy or pulmonary infiltrates either bronchoscopy (e.g., endobronchial ultrasound-guided transbronchial needle aspiration, endobronchial ultrasound-guided transbronchial needle aspiration) or thoracic surgery was performed. Both GCT patients with either tumor relapse or coexisting SLL were compared to GCT patients without SLL and tumor relapse. Results Twenty-nine patients suffered from suspected tumor relapse. Whereas thoracic relapses were suspected in 15 patients on chest computed tomography, thoracic relapse was confirmed in 5 cases by open surgery. In 2 cases open surgery yielded reactive lymphadenitis, and in 8 cases SLL was diagnosed either via EBUS-TBNA (n = 7) or thoracoscopic wedge resection plus lymphadenectomy (n = 1). With focus on overall survival, no relevant difference was found between all tested subgroups (P = 0.265; logrank test). Conclusions In GCT patients, the coexistence of noncaseating granulomatous disease is common. Minimal invasive bronchoscopic techniques can serve for the cytopathologic exclusion of malignant thoracic manifestations. In our monocenter patient group the coexistence of SLL did not have any prognostic impact on overall survival.

Introduction: Germ cell cancer (GCC) is a solid tumour entity with excellent prognosis. However, thoracic manifestations such as mediastinal lymph node involvement or lung metastasis occur and affect prognosis. The occurrence of sarcoidosis/sarcoid like lesions (SLL) in GCC patients is frequently described. To differentiate between SLL and metastasis tissue sampling in GCC patients with pulmonary nodules or hilar and/or mediastinal lymphadenopathy is necessary. Methods: To analyze the frequency of SLL, we evaluated histological and/ or cytopathological results of n=621 patients, who were investigated by EBUS during 2009 to 2015 at Munster University Hospital. Focus was put on the coincidence of GCC and noncaseating granuloma . Results: In total n=621 EBUS procedures were evaluated. In n=6 patients (1%) GCC was the main diagnosis. Five patients belonged to the IGCCCG good prognosis sub-group and one patient belonged to the IGCCCG poor prognosis sub-group. SLL lesions where diagnosed in n=5 GCC patients (0.8%). Metastatic disease was diagnosed in none of the GCC cases investigated by EBUS. In the only GCC patient without SLL lymphadenitis with anthracosis was diagnosed instead. Conclusion: Our retrospective analysis demonstrated the coincidence of GCC and SLL to be a frequent finding. EBUS-TBNA is a safe diagnostic approach to confirm SLL. Therefore, aggressive diagnostic approaches such as mediastinoscopy can be avoided. Still, both the prognostic and the immunologic impact of SLL in GCC remain unclear. Further studies should investigate the underlying biological mechanisms and the impact on prognosis.

Introduction: In NSCLC major improvements in diagnostics and treatment increased overall survival in the last decades. As a consequence, the number of patients with identified secondary malignancies has risen. Material and Methods: To identify clinicopathological characteristics and a potential prognostic impact of second order cancers, we retrospectively analyzed a pooled NSCLC patient cohort from two academic centers with focus on additional cancers. Results: Of 1012 NSCLC patients (median age 63.3 yrs, 27.2% female, 90.4% eversmokers, 49.9% adenocarcinoma, 49.2% TNM stage IV), 188 (18.6%) showed at least one additional malignancy [15/188 (8.0%) ≥ 2 additional cancers]. Of them, 128 (69.2%) were diagnosed ≥6 month prior NSCLC diagnosis (pre metachronous secondary cancer), 39 (21.1%) within 6 month before or after NSCLC diagnosis (synchronous secondary cancer), and 18 (9.7%) ≥6 month after NSCLC diagnosis (post metachronous secondary cancer). Genitourinary cancers (32.4%) and head&neck cancers (28.7%) were predominant. Besides stage, age, ECOG, BMI, and histology, multivariate Cox regression analysis revealed an improved survival for NSCLC patients with synchronous secondary cancers (HR 0.61 (95%CI 0.42-0.89), p=0.010) and post metachronous secondary cancers (HR 0.39 (95%CI 0.22-0.69), p Conclusion: Almost one out of five NSCLC patients suffered from secondary malignancies. Synchronous or post metachronous second order cancers, however, portray only one third of all secondary malignancies in NSCLC patients and display a substantial better prognosis. Future studies need to determine potential genetic or immunologic predispositions in this less aggressive NSCLC phenotype.

Objectives Several blood group-related carbohydrate antigens are prognosis-relevant markers of tumor tissues. A type 3 (repetitive A) is a blood group antigen specific for A 1 erythrocytes. Its potential expression in tumor tissues has so far not been examined. Material and methods We have evaluated its expression in normal lung and in lung cancer using a novel antibody (A69-A/E8). For comparison an anti-A antibody specific to A types 1 and 2 was used, because its expression on lung cancer tissue has been previously reported to be of prognostic relevance. Resected tissue samples of 398 NSCLC patients were analyzed in immunohistochemistry using tissue microarrays. Results and conclusions Expression of A type 3 was not observed in non-malignant lung tissues. A type 3 was expressed on tumor cells of around half of NSCLC patients of blood group A 1 ( p p =0.562), the expression of A type 3 by tumor cells indicated a highly significant favorable prognosis among advanced NSCLC patients ( p =0.011) and in NSCLC patients with lymphatic spread ( p =0.014). Univariate prognostic results were confirmed in a Cox proportional hazards model. In this study we present for the first time prognostic data for A type 3 antigen expression in lung cancer patients. Prospective studies should be performed to confirm the prognostic value of A type 3 expression for an improved risk stratification in NSCLC patients.