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Bei einer Schaumsklerosierungstherapie von Varizen können als Nebenwirkungen sowohl tiefe (TVT) als auch oberflächliche Beinvenenthrombosen (OVT) auftreten. Noch weitgehend unklar sind die Risikofaktoren, welche die Entstehung einer OVT oder TVT nach Schaumsklerosierung begünstigen. Das Ziel dieser retrospektiven Analyse war, anhand eines größeren Kollektivs von Patienten mit thromboembolischen Komplikationen sowohl patienten- als auch eingriffsbezogene Risikofaktoren für thromboembolische Komplikationen durch eine Schaumsklerosierung herauszuarbeiten.Insgesamt wurden 170 Patienten untersucht, die eine Schaumsklerosierung erhielten. Vor dem Stichtag 17. März 2020 wurden die letzten 85 Patienten mit thromboembolischen Komplikationen als Studiengruppe A und die letzten 85 Patienten ohne thromboembolische Komplikationen als Kontrollgruppe B nach Sklerosierung mit aufgeschäumtem Sklerosierungsmittel erfasst und verglichen.Patienten mit thromboembolischen Komplikationen hatten häufiger eine Thrombophilie (11/85 vs. 3/85). Die mittleren BMI-Werte waren in Gruppe A (25,9 ± 5,1) signifikant niedriger als in Gruppe B (28,0 ± 7,2) (P = 0,034). Thromboembolische Komplikationen zeigen sich nach Schaumsklerosierung eher am Unterschenkel (61/105) als am Oberschenkel (1/13) (P 0,001) dabei häufiger nach dorsaler als nach ventraler Schaumsklerosierung (39 von 47 vs. 5 von 40, P 0,001). Von den 39 thromboembolischen Komplikationen am dorsalen Unterschenkel waren 23 Muskelvenenthrombosen.Das Risiko für Muskelvenenthrombosen nach Schaumsklerosierung ist vor allem bei schlanken Patienten, welche am dorsalen Unterschenkel sklerosiert werden, erhöht.

Hydroxyurea and ruxolitinib are frequently used to treat myeloproliferative disorders, including polycythaemia vera, and chronic treatment is associated with many cutaneous adverse effects such as the development of aggressive non-melanoma skin cancer (NMSC). We report an 85-year-old man with a history of hydroxyurea- and ruxolitinib-treated polycythaemia vera who was referred for the management of progressively growing tumours on his scalp. Histopathology of the largest scalp lesion revealed a partly desmoplastic cutaneous squamous carcinoma with perineural invasion. Initial imaging revealed metastatic disease in cervical lymph nodes, bones and lungs. The scalp lesions were successfully treated with bleomycin-based electrochemotherapy. Under initial systemic therapy using four cycles of cetuximab, metastatic disease progressed. Following the approval by the health insurance, compassionate use of pembrolizumab monotherapy was initiated. After three cycles of pembrolizumab, however, metastatic disease further progressed and the patient finally died from global respiratory insufficiency. The present case exemplifies the cutaneous adverse effects of long-term hydroxyurea and ruxolitinib therapy, frequently resulting in highly aggressive NMSCs that are usually not responsive to systemic treatments even such as immune checkpoint inhibitors.

The relevance of Hedgehog signaling in Merkel cell carcinoma has only been addressed by a few studies with conflicting results. Thus, we aimed to establish the expression of Hedgehog signaling molecules in Merkel cell carcinoma to characterize causes of aberrant expression and to correlate these findings with the clinical course of the patients. Immunohistochemistry was performed for Sonic, Indian, Patched 1 (PTCH1) and Smoothened on patients' tumor tissue. Respective mRNA expression was analyzed in 10 Merkel cell carcinoma cell lines using quantitative real-time polymerase chain reaction. PTCH1 sequencing and DNA methylation microarray analyses were carried out on tumor tissues as well as cell lines. PTCH1 immunoreactivity in Merkel cell carcinoma was similar to that of basal cell carcinomas, which both significantly differed from PTCH1 immunoreactivity in healthy skin. Most PTCH1 mutations found were synonymous or without known functional impact. However, on average, the promoter regions of both PTCH1 were hypomethylated independently from PTCH1 gene expression or Merkel cell polyomavirus status. PTCH1 and GLI1/2/3 genes were differently expressed in different cell lines; notably, there was a significant correlation between GLI2 and PTCH1 mRNA expression. Similar to PTCH1 protein expression in patient tissues, PTCH1 gene expression in Merkel cell carcinoma cell lines is highly variable, but due to the similar methylation pattern across Merkel cell carcinoma cell lines, effects other than methylation seem to be the reason for the differential expression and PTCH1 appears to be upregulated by GLI as a classical Hedgehog target gene.

Background In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. Objectives To analyse the mRNA and protein expression of NCSTN, Notch1-3, PIK3R3 and AKT3 in HS. Methods Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. Results Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). Conclusion We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS.

Background: Lefty and Nodal are transforming growth factor β‐related proteins, which, beside their role in determination of laterality during embryogenesis, have also been linked with cancer progression. Objectives: Prompted by the observed significant left‐sided laterality of Merkel cell carcinoma (MCC), we addressed whether Lefty and Nodal are expressed in MCC and correlated expression patterns with clinical parameters such as MCC laterality and patient outcome. Methods: Expression of Lefty and Nodal in primary MCC was assessed in 29 patients by immunohistochemistry. The histology (H‐)score was calculated and correlated with clinical parameters. Results: The median (range) H‐score of Lefty and Nodal was 17.6 (0–291) and 74.9 (0.7–272), respectively. There was a significant correlation between Lefty expression and Nodal expression (correlation coefficient of 0.60, P = 0.0006). There was no significant correlation between Lefty expression and Nodal expression with either tumour laterality, gender, age, Merkel cell polyomavirus status, disease stage, anatomical localization of primary tumours or disease relapse. On univariate analysis, low Lefty expression and Nodal expression were significantly associated with MCC‐specific death (P = 0.010 and P = 0.019, respectively). On univariate analysis, low Lefty expression was the only significant independent predictor for MCC‐specific death (P = 0.025) as indicated by an odds ratio of 14 (95% CI: 1.43–137.33). Conclusions: Lefty and Nodal are frequently expressed in MCC, but not correlated with tumour laterality. Importantly, our data suggest that a low level of Lefty expression in primary MCC is a strong predictor of MCC‐specific death.

Usually, SCC lesions are surrounded by a number of clinically visible and non-visible (subclinical) areas of actinically damaged skin containing cells with dysplasia, and thus may be designated actinic dysplasia syndrome. The epithelial damage is caused mainly by UV radiation, inducing mutations in keratinocytes that may confer growth advantages resulting in preneoplastic fields. The development of visible dysplastic lesions (actinic keratosis - AK) and subsequent progression to invasive SCC requires further mutations in cancer-associated genes, like tumour suppressor genes and cell cycle regulators. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) represent a considerable advantage for the investigation of field cancerization. In addition, imaging allows the non-invasive monitoring of topical treatments for AKs. RCM provides in vivo horizontal skin sections with a high, 1-μm lateral resolution (similar to histopathology) but with a limited penetration (about 200 μm), which can hamper the visualization of important areas such as the dermal-epidermal junction. Conventional OCT has better penetration (1-2 mm) at the expense of a more limited resolution (much lower than histopathology). Line-field confocal OCT (LC-OCT) combines the high precision of RCM and the good penetration of OCT in a single device and therefore appears to be very useful in diagnosing/managing AKs.

Considering the rising incidence, cutaneous squamous-cell carcinoma (cSCC) has a high clinical relevance. In patients with localized cSCC, complete surgical resection is indicated. Radiotherapy should be performed in patients with non-resectable tumours or in patients who are not suitable for surgery. Systemic therapy is reserved for cSCC that are neither surgically nor radiotherapeutically curable due to their extensive local spread and/or local or distant metastasis. In the absence of prospective randomized phase 3 trials to evaluate and compare the efficacy and safety of chemotherapeutics, epidermal growth factor receptor (EGFR) inhibitors and anti-PD-1 antibodies, no final recommendation for systemic therapy can be given for patients with locally advanced or metastatic cSCC. Anti-PD-1 antibodies currently show promising results with response rates of up to 50% in both locally advanced and metastatic cSCC. Anti-PD-1 antibodies appear to achieve higher response rates compared with EGFR inhibitors, and the duration of response appears to be superior to both chemotherapy and EGFR inhibitors. Compared with chemotherapy, the side effect profile of anti-PD-1 antibodies appears to be favourable. Altogether, PD-1 inhibitors are expected to become the new standard of care for patients with locally advanced and metastatic cSCC. Currently, placebo-controlled clinical trials are investigating the adjuvant use of cemiplimab and pembrolizumab in patients undergoing resection and radiotherapy of high-risk cSCC. Patients not eligible for anti-PD-1 treatment, e.g. in organ transplant recipients, or in patients refractory to anti-PD-1 may be offered EGFR inhibitors and/or chemotherapies. Chemotherapies appear to be superior to EGFR inhibitors in terms of response rates, whereas EGFR inhibitors have a more favourable toxicity profile. EGFR inhibitors are therefore more suitable for multimorbid and/or frail elderly patients. By combining EGFR inhibitors with local therapy such as surgery or radiotherapy, response rates and duration of response may be improved.

BACKGROUND Mutations in kinetochore gene KNSTRN accelerate the development of cutaneous squamous cell carcinoma (SCC) and may correlate with different histological classifications of actinic keratosis (AKs). OBJECTIVE To determine KNSTRN gene mutation frequency in healthy skin (HS), actinically damaged skin (ADS), in AKs with different histomorphological gradings and invasive SCCs. METHODS All samples were histologically evaluated. AK lesions were additionally classified according to their upwards (AK I-III) and downwards (PRO I-III) directed growth pattern. Mutation analyses of all samples were performed using the Sanger method. RESULTS With one exception, all detected mutations in KNSTRN gene showed an alanine-to-glutamate substitution at codon 40 (p.Ala40Glu). p.Ala40Glu mutation was found in 6.9% (2/29) of HS, in 16.1% (5/31) of ADS, in 18.3% (20/109) of AKs and in 30.0% (9/30) of invasive SCCs. Further stratification of AKs using the common AK classification of Rowert-Huber revealed the p.Ala40Glu mutation in 14.7% (5/43), 13.3% (4/30) and 24.4% (11/45) (AK I, II and III). In contrast, the new PRO classification showed a distribution of 3.6% (1/28) in PRO I, 21.7% (13/60) in PRO II and 28.6% (6/21) in PRO III. Mutation frequency in HS showed significant differences compared to AKs classified as PRO III and invasive SCCs (P

Background Dysregulation of microRNAs (miRNAs) key regulators may contribute to the pathogenesis of malignancies. miRNA machinery genes such Dicer and Drosha have been reported to be biomarkers in different cancer types. Objectives We aimed to evaluate Drosha and Dicer protein expression in cutaneous T-cell lymphoma (CTCL). Methods We performed Drosha and Dicer immunohistochemistry in 45 patients with mycosis fungoides and subtypes. Drosha and Dicer expression scores were correlated with clinical parameters including disease-specific death (DSD), stage of disease and different laboratory data. Uni- and multivariate statistics were performed. Results On univariate analysis, elevated serum LDH and low Drosha expression were significantly associated with advanced stage (P = 0.032 and 0.0062, respectively) and lymphoma-specific death (LSD; P = 0.017 and P = 0.005, respectively). Moreover, elevated circulating CD4+/CD26- lymphocytes were significantly associated with advanced stage (P = 0.032) and DSD (P = 0.0098). On multivariate analysis, low Drosha expression remained in the logistic regression model as significant independent predictor for advanced disease stages [P = 0.013; odds ratio: 5 (confidence interval) CI 1.3-19.3]. Moreover, low Drosha expression (P = 0.026) and elevated LDH (P = 0.025) remained as significant independent predictors for DSD with odds ratios of 13.5 (CI 1.3-134.4 and 8.7 CI 1.3-57.2, respectively). Conclusions Low Drosha expression is an independent predictor for advanced stage as well as LSD in CTCL patients indicating a tumour suppressor gene function of Drosha in this disorder.

BACKGROUND Actinic keratoses (AKs) can histologically be classified by the extent of atypical keratinocytes throughout the epidermis or their pattern of basal proliferation. Currently, no data on the inter-rater reliability of both scores is available. OBJECTIVE To evaluate the inter-rater reliability of the two classification schemes; histological grade (AK I-III) and basal proliferation (PRO I-III). METHODS Histological images of 54 AKs were classified by 21 independent dermatopathologists with regard to basal proliferation (PRO I-III), histological grade (AK I-III) and assumed risk of progression into invasive carcinoma. RESULTS Overall, of the 54 AKs 16.7% (9/54) were classified as AK I, 66.7% (36/54) as AK II, and 16.7% (9/54) as AK III. With regards to basal growth pattern, 25.9% (14/54) were classified as PRO I, 42.6% (23/54) as PRO II, and 31.5% (17/54) as PRO III. We observed a highly significant inter-rater reliability for PRO-grading (P < 0.001) which was higher than for AK-grading (Kendall's W coefficient: AK = 0.488 vs. PRO = 0.793). We found substantial agreement for assumed progression risk for AKs with worsening basal proliferation (k = 0.759) compared to moderate agreement (k = 0.563) for different AK-gradings. CONCLUSIONS Histological classification of basal growth pattern (PRO) showed higher inter-rater reliability compared to the established classification of atypical keratinocytes throughout epidermal layers. Moreover, experienced dermatopathologists considered basal proliferation to be more important in terms of progression risk than upwards directed growth patterns. It should be considered to classify AKs according to their basal proliferation pattern (PRO I-III).

BACKGROUND/OBJECTIVES Histological heterogeneity within distinct actinic keratosis (AK) lesions has been described and might serve as an additional feature of AKs. We aimed to investigate and quantify the histological heterogeneity of AKs regarding different grading systems. METHODS AND MATERIAL We assessed the histology of 3 mm biopsies of AK lesions located on the scalp or face. We documented basal proliferation (PRO I-III), histological grade (AK I-III) and determined the overall classification of each lesion. RESULTS Of the 305 lesions included, 48 (15.7 %) lesions were classified as AK I, 152 (49.8 %) as AK II and 105 (34.4 %) as AK III. 33 AKs (10.8 %) showed no basal proliferation, 94 (30.8 %) were graded as PRO I, 99 (32.5 %) as PRO II and 79 (25.9 %) as PRO III. One histological grade and basal growth pattern per lesion was observed in 94 (30.8 %) and 104 (34.1 %) cases respectively, two grades in 170 (55.7 %) and 168 (55.1 %) cases, and three grades in 41 (13.4 %) and 33 (10.8 %) cases (Chi-squared test, p

Aktinische Keratosen sind als intraepitheliale Proliferation atypischer Keratinozyten definiert und können in ein invasives Plattenepithelkarzinom übergehen, welches sich in der Folge zu einer potenziell lebensbedrohlichen Krankheit entwickeln kann. Die Inzidenz von AK hat in den letzten Jahrzehnten aufgrund eines veränderten Freizeitverhaltens der Bevölkerung und des demographischen Wandels in den Industrienationen deutlich zugenommen. Derzeit wissen wir jedoch nicht, ob und wann eine AK in einen invasiven Tumor übergeht, sodass die konsequente Behandlung der Feldkanzerisierung ein wichtiger Bestandteil zur Vermeidung eines möglichen Progresses darstellt. Neben einem breiten Armamentarium an interventionellen und medikamentösen Therapieoptionen kommt dabei der primären Prävention insbesondere durch konsequenten Sonnenschutz eine entscheidende Bedeutung zu. Weitergehend wären klinische, histomorphologische oder molekularbiologische Klassifikationen wünschenswert, die eine zuverlässige Risikostratifizierung der Patienten ermöglichen würden. Damit ließe sich, auch unter sozioökonomischen Gesichtspunkten, eine Über- bzw. Untertherapie der steigenden Patientenzahlen zukünftig vermeiden und individualisierte, bedarfsadaptierte Therapiekonzepte erstellen.

Actinic keratoses (AKs) are defined as intraepithelial proliferation of atypical keratinocytes. Given their potential for progression to invasive squamous cell carcinoma, they may eventually evolve into a life-threatening disease. In recent decades, there has been a significant increase in the incidence of AKs, primarily due to changes in recreational activities and demographic trends in industrialized countries. As it is currently impossible to predict if and when a given AK might progress to invasive carcinoma, rigorous treatment of field cancerization is a key component in preventing potential progression. In addition to a broad armamentarium of procedures as well as pharmaceutical treatment options, primary prevention through diligent UV protection likewise plays a crucial role. New clinical, histomorphological, or molecular classifications are needed to be able to reliably stratify patients based on their individual risk. Especially in light of socio-economic aspects, such a step might prevent over- and undertreatment of an ever-growing patient population and help develop treatment concepts based on individual patient needs.

BACKGROUND Koebnerized non-melanoma skin cancer following skin trauma represents a rare and obscure event. OBJECTIVES To study molecular pathological parameters in koebnerized squamous cell carcinomas (K-SCCs) occurring after complete tumour removal. METHODS We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long-term azathioprine therapy. Both patients rapidly developed several K-SCCs following histopathologically proven complete excision of cutaneous SCCs. We performed immunohistochemistry for p53, p16, Ki-67, TET-2, IDH-2, 5-hmc and 5-mc. PCR was carried out for the detection of human papilloma viruses. Mutation analysis was performed for BRAF, K-RAS and EGFR. RESULTS All lesions investigated were negative for HPV DNA. Mutations were not detected. Healthy appearing skin of both patients showed relatively high Ki-67, p16 and p53 expression which was comparable to the expression observed in primary SCCs as well as K-SCCs. Protein expression of Ki-67, p16 and mutant p53 was barely detected in the specimens of the healthy controls. A decreased protein expression of TET-2 enzyme was seen in all tumours and healthy appearing skin when compared to the skin of healthy controls. CONCLUSIONS We observed two patients with K-SCCs developing under DMF treatment. In healthy appearing skin of patients with K-SCCs, wound healing processes, including induction of proliferation and growth factor release, might promote the growth of preneoplastic keratinocytes and cancer formation on the basis of pre-existing altered epigenetic pathways and cell cycle dysregulation. Although fumarates can reduce TET-2 expression, the role of DMF intake in the development of K-SCCs remains unclear.

Background Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied. Objective To investigate the extent of atypical keratinocytes throughout the epidermis and variation in basal growth patterns of AK. Methods AK lesions occurring on the head/face from patients seen in routine practice were assessed histologically. We determined histological grade (AK I-III), basal growth patterns of atypical keratinocytes (crowding, budding and papillary sprouting) and accompanying parameters. Results Of the 246 lesions included, 28.0% were histologically classified as AK I, 46.7% as AK II and 25.2% as AK III. Approximately 26.4% of the basal growth patterns were classified as crowding (pro I), 49.6% as budding (pro II), 17.9% as papillary sprouting (pro III) and 6.1% without basal directed growth. No significant correlation of the histological AK I-III grading and underlying growth patterns was observed (P = 0.4666). However, adnexal structure involvement (OR = 2.37; 95% CI 1.21-4.65), infiltration (OR = 2.53; 95% CI 1.31-4.90) and increased number of vessels (OR = 2.56; 95% CI 1.42-4.65) were independent positive predictive markers for pro II and pro III basal growth patterns. Conclusions Basal growth patterns (pro I-III) in AK do not correlate with the established AK I-III histological grading system. Besides the degree of upward extension, varying degrees of downward extension exist. Histological classification should consider both, upwards and downward growth patterns when assessing AK.

Actinic keratoses (AKs) are intraepithelial atypical proliferations of keratinocytes that develop in skin that has undergone long-term exposure to ultraviolet radiation. Given the ageing population and an increasing prevalence of AK, the socio-economic burden of AK is likely to rise over the coming years. Areas of subclinical (non-visible) sun damage in the periphery of visible AK lesions contain the same genetic changes as those found in the lesions themselves, and are known as areas of field cancerization. AK lesions and the field are associated with an increased risk of skin cancer, including invasive squamous cell carcinoma. Although effective in clearing visible AK, lesion-directed therapies do not address field cancerization and can lead to high recurrence rates. In contrast, field-directed therapies, such as ingenol mebutate, imiquimod and diclofenac, can clear both visible and subclinical AK lesions and reduce the development of new lesions in the treated field. Additionally, preclinical studies suggest that field therapy may prevent or delay the recurrence of non-melanoma skin cancer. AK treatment guidelines now recognize the importance of treating the field in patients with AK, and adaptation of treatment guidelines into clinical practice is warranted. Physician and patient education around the consequences of leaving the field of cancerization untreated is necessary in order to reduce the increasing burden associated with AK.

Hintergrund Die Synkanzerogenese am Hautorgan, wissenschaftlich unstrittig, spiegelt sich im monokausal geleiteten Berufskrankheiten (BK)-Recht nicht wider. Nichtmelanozytare Hauttumoren und deren Vorlauferlasionen konnen nur nach Einzelprufung der BK-Nrn. 5103 und 5102 anerkannt werden. Methodik Retrospektive Auswertung von 28 zwischen September 2012 und September 2015 begutachteten Fallen (Altersmedian 72,5 J.) mit nichtmelanozytaren Hauttumoren und deren Vorlauferlasionen und arbeitsbedingter Exposition gegenuber naturlicher UV-Strahlung und polyzyklischen aromatischen Kohlenwasserstoffen. Ergebnisse In allen 28 Fallen sahen wir die arbeitstechnischen Voraussetzungen nach den BK-Nrn. 5103 und 5102 als erfullt an. In 26 Fallen (93 %) empfahlen wir die Hautkrebserkrankung als BK-Tatbestand nach den Nrn. 5103 und 5102 anzuerkennen. Dem folgte der Unfallversicherungstrager in vier Fallen. Achtmal wurde die Anerkennung nur nach BK-Nr. 5103, zehnmal nur nach BK-Nr. 5102 und viermal gar nicht ausgesprochen. Schlussfolgerungen Bei nichtmelanozytaren Hauttumoren oder deren Vorlauferlasionen an UV-exponierten Hautarealen mit ausreichend kumulativer arbeitsbedingter naturlicher UV-Strahlenexposition und bei arbeitsbedingter Exposition gegenuber polyzyklischen aromatischen Kohlenwasserstoffen sollten mittels BK-Anzeige die "BK-Nrn. 5103 und 5102 im Sinne der Synkanzerogenese" gemeldet werden. Neben der gerechteren Wiedergabe der Arbeitsplatzrealitaten in einem solchen Feststellungsverfahren kann es dann im Konkreten auch zur Anerkennung von Basalzellkarzinomen kommen, die ansonsten, bei alleiniger Prufung der BK-Nr. 5103, herausgerechnet wurden.

SummaryBackground Though scientifically undisputed, cutaneous syncarcinogenesis is not reflected in German occupational disease (OD) regulations, which tend to be guided by the tenet of monocausality. Recognition of nonmelanoma skin cancer (NMSC) and its precursor lesions as OD requires individual assessment as to whether the requirements pursuant to either OD 5103 (occupational exposure to natural UV radiation) or OD 5102 (occupational exposure to polycyclic aromatic hydrocarbons) are fulfilled. Methods Retrospective analysis of 28 patients (median age 72.5 years) with NMSC and respective precursor lesions who had been occupationally exposed to natural UV radiation and polycyclic aromatic hydrocarbons. All cases had undergone expert medical assessment between September 2012 and September 2015. Results According to our assessments, all 28 cases met the occupational requirements pursuant to OD 5103 and 5102. In 26 cases (93 %), we recommended recognition of skin cancer as occupational disease pursuant to both OD 5103 and OD 5102. The competent occupational insurance association (BG) followed our recommendation in four cases. In eight cases, recognition was solely based on OD 5103; in ten cases, only on OD 5102. Four cases were denied recognition. Conclusions Following adequate cumulative occupational exposure to natural UV light as well as occupational exposure to polycyclic aromatic hydrocarbons, NMSC or its precursor lesions arising in UV-exposed areas should be reported to the competent occupational insurance association as “OD 5103 and 5102 in terms of syncarcinogenesis”. Apart from the fact that the ensuing recognition proceedings will be able to more adequately reflect real-life workplace conditions, filing a report pursuant to both ODs also allows for recognition of basal cell carcinoma as occupational disease. According to current regulations, this would not be possible, if the assessment were solely based on OD 5103.

BACKGROUND AND OBJECTIVES Cutaneous squamous cell carcinoma (SCC) is known for its capacity to metastasize via lymphatic vessels. In recent studies, the level of lymphangiogenesis has been reported as a potential prognostic factor for several skin tumors. The aim of this study was to quantify lymphangiogenesis in SCC using either computer-assisted image analysis or the Chalkley count technique. Vascular parameters were evaluated and compared with respect to their predictive power for tumor metastasis. PATIENT AND METHODS In this case-control study, clinical and histological data of 15 metastatic and 15 nonmetastatic SCC patients were retrospectively analyzed. SCC samples were immunostained for the lymphatic endothelial marker D2-40 and the panvascular marker CD31, and analyzed using computer-assisted morphometric image analyses within hot spots as well as the digitalized Chalkley counting method. RESULTS Lymphatic vessel density, relative lymphatic vessel area, and lymphatic Chalkley count were significantly elevated in metastatic SCC. Tumor thickness was significantly higher in metastatic SCC, and had the highest predictive power for metastatic disease. Tumor thickness was a significant predictor of lymphangiogenic parameters. CONCLUSIONS Lymphangiogenesis is elevated in metastatic SCC but its extent is influenced by tumor thickness. Tumor thickness remains the most reliable predictive factor for metastatic disease.

Hintergrund und ziele Kutane Plattenepithelkarzinome (SCC) sind bekannt fur ihre Fahigkeit, uber Lymphgefase zu metastasieren. In neueren Studien wird das Ausmas der Lymphangiogenese als moglicher prognostischer Faktor bei einigen Hauttumoren genannt. Ziel dieser Studie war die Quantifizierung der Lymphangiogenese bei SCC entweder durch computergestutzte Bildanalyse oder mithilfe der Zahlmethode nach Chalkley. Gefasparameter wurden im Hinblick auf ihre Vorhersagekraft fur die Bildung von Tumormetastasen beurteilt und verglichen. Patienten und methoden In dieser Fallkontrollstudie wurden die klinischen und histologischen Daten von jeweils 15 SCC-Patienten mit bzw. ohne Metastasen retrospektiv analysiert. In den SCC-Proben wurde der fur das Lymphendothel spezifische Marker D2-40 und der pan-vaskulare Marker CD31 immunhistochemisch angefarbt und durch computergestutzte morphometrische Bildanalyse in Hotspots sowie mithilfe der digitalisierten Zahlmethode nach Chalkley analysiert. Ergebnisse Die Dichte von Lymphgefasen, die relative Lymphgefasflache und die mit der Chalkley-Methode ermittelte Zahl an Lymphgefasen (Chalkley-Count) waren bei metastasierten SCC signifikant erhoht. Die Tumordicke war bei metastasierten SCC signifikant hoher und besas die hochste Vorhersagekraft fur eine Metastasierung. Die Tumordicke war ein signifikanter Pradiktor fur Lymphangiogeneseparameter. Schlussfolgerungen Die Lymphangiogenese ist bei metastasierten SCC erhoht, doch ihr Ausmas wird von der Tumordicke beeinflusst. Die Tumordicke bildet weiterhin den zuverlassigsten pradiktiven Faktor fur die Metastasierung.

Background There are several clinical and histological classification systems for grading actinic keratosis (AK) lesions. The Olsen clinical classification scheme grades AK lesions according to their thickness and degree of hyperkeratosis (grades 1–3). The Roewert-Huber histological classification system grades AK lesions based on the extent of epidermal atypical keratinocytes (AK I–III). Objective The aim of this study was to determine whether there is a correlation between these clinical and histological AK classification schemes. Methods One AK lesion from patients in three pivotal clinical studies and routine practice was assessed clinically and histologically. A match in grading was defined as Olsen grade 1 being classified histologically as AK I, Olsen grade 2 as AK II and Olsen grade 3 as AK III. Results Of the 892 lesions included, 29.0% were classified as Olsen grade 1, 59.6% as Olsen grade 2 and 11.3% as Olsen grade 3; 19.2% were histologically classified as AK I, 69.6% as AK II and 11.2% as AK III. Only 480 lesions (53.8%) had a matching clinical and histological classification. Of these matches, most were ‘Olsen grade 2 = AK II’ (83.1%). The Spearman's rank correlation coefficient for clinical and histological classification was r = 0.0499 (P = 0.137). Conclusions Clinical classification of AK lesions using the system of Olsen does not accurately match histological classification of the same lesions using the system of Roewert-Huber. Consequently, it is not possible to draw conclusions about the histology of AK lesions from their clinical appearance. This finding reinforces the need to treat all AK lesions as well as field cancerization.

Patients with obsessive-compulsive (OCD) and related disorders - primarily trichotillomania, body dysmorphic disorder, and skin picking disorder - frequently present to dermatologists due to associated hair and skin symptoms. It is therefore crucial that dermatologists be familiar with these disorders. In this review article, we provide an update on clinical features, neurobiology factors, and treatment options for OCD spectrum disorders. Employing PubMed and Cochrane Library databases, a selective literature search was conducted using keywords related to dermatological disorders within the OCD spectrum. OCD and its related disorders share several phenomenological as well as pathophysiological similarities, thus warranting their classification within a separate nosological category of psychiatric disorders. Another similarity of OCD spectrum disorders is the frequent concurrence of hair and skin diseases. Besides symptomatic dermatological treatment, the combination of psychotherapy (behavioral therapy) and psychopharmacotherapy (SSRIs) may be helpful. Although recent insights into OCD have contributed to a better understanding and treatment thereof, more research is required, especially with respect to OCD spectrum disorders, for which large controlled treatment studies are still lacking.

Zusammenfassung Patienten mit einer Zwangsstorung und verwandte Storungen, zu denen die Trichotillomanie, die korperdysmorphe Storung und die Dermatillomanie (skin picking) in erster Linie zahlen, konsultieren aufgrund der dabei auftretenden Haar- und Hautsymptome haufig einen Dermatologen. Es ist somit wichtig, auch von dermatologischer Seite uber diese Erkrankungen gut informiert zu sein. In dieser Ubersichtarbeit werden aktuelle Aspekte zur Klinik, Neurobiologie und Therapie der Zwangsspektrumsstorungen dargestellt. Es wurde eine selektive Literaturrecherche (PubMed und Cochrane Library) mit Suchbegriffen bzgl. dermatologischer Storungen bei Zwangsspektrumsserkrankungen durchgefuhrt. Die Zwangsstorung und die ihr verwandten Storungen haben zahlreiche phanomenologische und pathophysiologische Gemeinsamkeiten, so dass ihre Einordnung in einer eigenen nosologischen Kategorie psychiatrischer Storungen begrundet ist. Eine weitere Gemeinsamkeit der Zwangsspektrumsstorungen ist das haufig gleichzeitig bestehende Vorhandensein von Haut- und/oder Haarerkrankungen. Neben der symptomatischen, dermatologischen Behandlung kann eine Kombination von Psychotherapie (Verhaltenstherapie) und Psychopharmakotherapie (SSRIs) hilfreich sein. Obwohl das Wissen uber die Zwangsstorung einiges zum Verstandnis und zur deren besseren Behandlung beigetragen hat, besteht weiterhin Forschungsbedarf vor allem im Bereich der Zwangsspektrumsstorungen, fur die grose kontrollierte Behandlungsstudien fehlen.

Background Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. Objectives The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. Methods The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. Results Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. Conclusions International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

The new target for the treatment of actinic keratosis (AK) is the detection and clearance of clinical and subclinical lesions across an entire sun-exposed field. This is because patients with AK have field cancerization as ultraviolet light affects the entire sun-exposed area and because it is not possible to predict which AK lesions will progress into invasive squamous cell carcinoma. To fully assess the effectiveness of field-directed therapies against the full burden of AK, a new efficacy concept has been developed which is based on the reduction in lesions from Lmax, or the maximum lesion count during treatment. This new parameter enables the efficacy of a field-directed therapy against both clinical and subclinical lesions to be assessed. Imiquimod 3.75% is a novel field-directed therapy which uniquely can detect and clear both clinical and subclinical lesions across a large sun-exposed field such as the full face or balding scalp, and so far is the only AK treatment to have had its efficacy assessed with the Lmax concept. The detection of subclinical lesions is evidenced by an increase in lesion count during each of the 2-week treatment cycles, which are separated by a 2-week treatment-free interval. The median percentage reduction in lesions from Lmax with imiquimod 3.75% is 92%, and the effective clearance of both clinical and subclinical lesions leads to sustained lesion clearance for at least 1 year. Imiquimod 3.75% has an acceptable tolerability profile. Rest periods from treatment may be taken if required to manage local skin reactions, with no loss in efficacy. In conclusion, Lmax and imiquimod 3.75% together set the new standard in the management of patients with AK.

Actinic keratosis (AK) is characterized by high prevalence and the risk to proceed to squamous cell carcinoma (SCC). Cyclooxygenase-2 (COX-2)-mediated prostaglandin E2 (PGE (2) ) synthesis has been reported in AK and SCC, and the COX inhibitor diclofenac in hyaluronic acid (diclofenac/HA) was approved for AK therapy. Its mode of action, however, remained to be unravelled. In the present study, diclofenac resulted in reduced PGE (2) levels in apoptosis-sensitive cutaneous SCC cell lines (SCL-II, SCC-12, SCC-13) whereas no PGE (2) and no COX-2 expression was detectable in a SCC cell line resistant to apoptosis induction (SCL-I). Activation of mitochondrial apoptosis pathways was evident in SCC cells owing to loss of the mitochondrial membrane potential and release of the mitochondrial factors cytochrome c and apoptosis-inducing factor. Characteristic proapoptotic changes at the level of Bcl-2 proteins occurred in sensitive cells, as upregulation of Bad and downregulation of Mcl-1 and Bcl-w. In contrast, Bad was already high, and Mcl-1 and Bcl-w were already low in resistant SCL-I, even without treatment, which may be explained by the lack of PGE (2) . An antiapoptotic downregulation of proapoptotic Bcl-2 proteins Noxa and Puma was, however, also seen in SCL-I, suggesting here pathways independent of COX-2. The regulations of Mcl-1 and Bad were also reproduced in SCC cells by the more selective COX-2 inhibitor celecoxib, thus further underlining the specific role of COX-2. The findings illuminate the mode of action of diclofenac/HA in SCC cells as well as principles of their resistance, which may allow further adaptation and improvement of the new therapy.

Summary Background: The efficacy of topically applied diclofenac 3 % in combination with hyaluronic acid 2.5 % in the treatment of actinic keratoses (AKs) has been demonstrated in several clinical studies, but the exact mode of action is still unclear. This study evaluates the potential molecular and cellular main modes of action of topically applied diclofenac in the treatment of AKs. Patients and methods: In this prospective study 20 male patients with AKs were treated for 90 days with topically applied diclofenac 3 %/hyaluronic acid 2.5 %. Before and after treatment, skin biopsies were taken from the treatment area and were investigated histologically and immunohistochemically as well as compared to healthy skin. For this purpose, markers for inflammation (COX-2, CD3, CD8), apoptosis (p53), cell cycle arrest (p53, p21), proliferation (Ki67), and angiogenesis (CD31) were examined. Results: The immunohistochemical analysis demonstrated a significant decrease in expression of COX-2, CD3 and CD8. Furthermore, there was a clear reduction of CD31 expression as a marker for angiogenetic processes. Additionally, there was a tendency toward a reduction in markers for proliferation and apoptosis. Conclusions: The efficacy of diclofenac 3 %/hyaluronic acid 2.5 % in the treatment of AKs is probably due to anti-inflammatory and anti-angiogenic effects, potentially associated with anti-proliferative and apoptosis-inducing underlying mechanisms.

Multiphoton tomography (MPT) is an in vivo imaging technique with very high spatial resolution and efforts are made to combine MPT with other non-invasive imaging methods. The goals of the present study were the description of the features of different dermatological entities as seen in MPT and confocal laser scanning microscopy (CLSM) comparison of these two novel techniques and the 'classical' diagnostic measures visual inspection, dermoscopy and histology with respect to the strengths and weaknesses of the different methods and the potential benefit from their combined implementation. After study approval by the local Ethics Committee, 47 patients (31 male, 16 female, age range: 24-88 years) were recruited from the Department of Dermatology of the University Hospital Jena. In this work, we present an illustrative selection of eleven cases from a clinical study combining in vivo MPT with in vivo CLSM. The patients presented with a broad range of dermatological disorders including seborrheic keratoses, angioma, actinic keratoses, melanocytic nevi, malignant melanoma, psoriasis, pemphigus vulgaris and scarring. Both methods, CLSM and MPT, were found to be suitable for in vivo imaging of superficial skin layers and may therefore be useful in dermatological practice for the diagnosis of skin diseases. However, both methods differ in their technical and physical principles. Thus, despite of many similarities concerning the morphological presentation of cells and tissues, important differences are recognized. Synergies of the combination of CLSM and MPT may be obtained by combined implementation in order to benefit from the fast overview given by CLSM and the detailed imaging of skin structures by MPT.

Background: Actinic keratoses (AK) are carcinomata in situ with the potential to develop into invasive carcinoma. Several studies have demonstrated that 3% diclofenac in 2.5% hyaluronic acid gel (HA) is effective and well tolerated in the treatment of AK. To date there are no large randomized multicentre trials with treatment durations longer than 90 days and histopathological control of treatment outcome. Objective: The aim of this study was to investigate whether a prolonged treatment with diclofenac in HA of 6 vs. 3 months adds to the efficacy in treatment for AK and if this will influence tolerability and quality of life (QoL). Methods: This was a multicentre, randomized open-label study in which 418 patients with mild to moderate AKs were randomized into two treatment groups. Group A received diclofenac in HA for 3 months and group B for 6 months. Treatment efficacy was assessed by size measurement and a final biopsy of a defined marker AK. Quality of life was measured using the Dermatology Life Quality Index questionnaire. Results: Clinical complete clearance was observed in 40% in group A and in 45% in group B (P = 0.38). Histopathological clearance was confirmed in 30% in group A and in 40% in group B (P = 0.16). Treatment was well tolerated and QoL was significantly improved after treatment in both treatment groups. Conclusion: Treatment with diclofenac in HA is effective and well tolerated during a treatment period of 3 months as well as 6 months. Prolongation of the treatment duration did not significantly affect treatment outcome.

Background Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid. Methods Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM. Results Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination. Conclusions Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases.

Background: Histopathologically, basal cell carcinoma (BCC) is characterized by basaloid tumor nodules of varying size showing peripheral palisading of cells and nuclei, and separation from surrounding stroma by optically empty appearing clefts. These are usually regarded as an artifact, occurring during routine tissue processing. Recently, reflectance confocal microscopy (RCM) has been applied for noninvasive, in vivo evaluation of BCC. Besides other features, small areas of low refractility separating tumor islands from the surrounding tissue can be observed in vivo, suggesting that the presence of amorphous material like mucin might be the causal factor for these clefts. Methods: A total of 13 BCCs were studied by RCM and histopathological techniques. Staining was performed with Alcian blue for the detection of peritumoral mucin. Correlation between RCM images and histopathological samples was studied, and the diameter of hyporefractile areas on RCM as well as the thickness of peritumoral mucin was measured. Results: Good correlation was seen between dark areas on RCM and thickness of peritumoral mucin with a mean diameter of 14 μ m( RCM) and 11.44 μm (histopathology), respectively. Pearson correlation coefficient was 0.605 (p < 0.0001). Conclusions: Our results show that the peritumoral cleft-like spaces seen in BCC on histopathology exist in vivo, and correspond to the peritumoral mucin deposition.

Mammalian target of rapamycin inhibitor use is associated with numerous adverse events, including dermatologic and mucosal problems. Awareness of these complications, which clinically manifest across a severity spectrum from minor through severe and may occur at varied time points after initiation of sirolimus therapy, can be useful to clinicians in both managing these events and determining the appropriate intervention(s) for patients. This manuscript examines the dermatologic and mucosal problems associated with mammalian target of rapamycin inhibitor use, reviews the literature, and provides personal experiences regarding the management and treatment of these adverse events.

Background: Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK). Objectives: To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK. Methods: Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (λem ≈ 630 nm; 37 J/cm2). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events. Results: A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the ‘best treatment’. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range. Conclusions: The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.

Squamous cell carcinoma (SCC) of the skin is a malignant locally destructive epithelial tumor which uncommonly metastasizes. SCC is the second most common skin tumor following basal cell carcinoma. It has shown a rapid increase in increase in the white population. The most important etiologic factor is chronic UV exposure, especially in individuals sensitive to UV light. Risk factors for developing SCC include actinic keratoses, advanced age, high cumulative sun exposure, and lightly pigmented skin. The most important risk factor is the presence of actinic keratoses In Great Britain, the age-dependent prevalence of actinic keratoses is estimated at 15% for men and 7% for women. Transition from actinic keratosis to SCC occurs in about 5% of lesions. In addition to the malignant transformation induced by UV irradiation, other etiologic factors include chronic wounds and inflammatory lesions such as leg ulcers, burns, and other scars, as well as lichen planus and bullous dermatoses. Both arsenic exposure and ionizing radiation can also induce SCC. The incidence of SCC is markedly increased in immunosup-pressed individuals, and the tumors are more aggressive in this population. This is true for patients with iatrogenic immunosuppression after organ transplantation, hematologic malignancies, chemotherapy and HIV infection. The malignant transformation of keratinocytes is triggered by carcinogenic human papilloma viruses which are more common in immunosuppressed patients. Genetic syndromes with increased incidence of SCC include albinism, xeroderma pigmentosum and Muir-Torre syndrome. In central Europe the incidence of SCC was estimated at 20-30 / 100,000 yearly during the 1990s. About 90% of the tumors are on the face. The average age at presentation is 70 years; men are more often affected than women. Metastasis occurs in around 5% of patients and almost always involves the regional lymph nodes. The 5-year survival with metastases is 25-50%. The clinical presentation of SCC is heterogenous, although not as varied as basal cell carcinoma. Invasive SCC can arise from erythematous patches or hyperkeratotic plaques (actinic keratosis, Bowen disease). Most SCC are nodular with crusting and often ulceration. They grow

The diagnostic meaningfulness of patch tests with house dust mite allergens is still questionable. Our own impression has been that positive results with a dermatophagoides mix may occur preferentially in patients with a generally enhanced responsiveness to contact allergens. To check this, all of our patients allocated to patch testing with the standard series were additionally patch tested with a dermatophagoides mix by the same technique that was used for standard contact allergens. Out of 571 patients tested, 188 showed delayed responses to this mix that were indistinguishable from typical allergic patch test reactions but of no apparent clinical relevance. No relationship was found between positive dermatophagoides patch tests and an atopic disposition of the patients or characteristics of their eczema. However, 64.4% of the patients with a positive dermatophagoides patch test showed a response to at least 1 contact allergen of the standard series, compared to only 56.4% of the patients without a positive dermatophagoides reaction (p < 0.05). The reactivity to the mite mix was not related to the responsiveness towards any particular contact allergens. We suppose that some unidentified factors may contribute to positive reactions to the dermatophagoides mix that may also favour an enhanced general responsiveness to contact allergens.

Objective To report early clinical experience with intraurethral instillation of 5-aminolevulinic acid (ALA) for the detection of clinical lesions (condyloma acuminata) and subclinical human papillomavirus (HPV) lesions of the urethra, not visible by conventional endoscopy. Subjects and setting Eighty-four men with clinical diagnosis of condyloma acuminata were examined for urethral HPV lesions at the Department of Urology, Ludwig Maximilian University, Munich, Germany. Methods The anogenital areas of the patients were thoroughly examined using a magnifying glass before and after application of 5% acetic acid. Conventional as well as fluorescence urethroscopy were performed 1 h after topical application of 0.1% ALA for 15 min. A sensitive colour charge-coupled device camera for fluorescence video inspection was used with spectral analysis. Biopsies were taken for histological examination and HPV detection by polymerase chain reaction (PCR). Results Forty-three of 84 men attending our clinic for condyloma acuminata had clinical HPV lesions of the urethra. Condylomas of the proximal urethra were found by conventional endoscopy in eight patients. Fluorescence urethroscopy detected additional subclinical lesions in 13 men. All lesions were HPV infections of the urethra confirmed histologically or by PCR. In nine of these subclinical urethra lesions low-risk HPV types (HPV6, 11, 34) were found. Four lesions were associated with high-risk types (HPV18, 31, 52, 58). Conclusions Fluorescence urethroscopy is a promising diagnostic procedure for detecting subtle clinical and subclinical HPV lesions of the urethra, that are normally not visualized by conventional endoscopy. Generally, urethroscopy is recommended in all cases of externally visible condylomas of the urethra after therapy.

Keywords: cervical dysplastic lesions; human papillomavirus; polymerase chain reaction; routine gynecologic screening