Concentration distribution of more than 100 drugs and metabolites in forensic hair samples.

Drug testing in hair can complement conventional blood and urine analysis as it enlarges the window of detection and may allow a differentiation of heavy from moderate or rare use. Databases of drug concentrations in biological matrices are a valuable support in interpreting analytical results. In forensic toxicology, several databases exist especially for blood/serum samples. In the present paper, the concentration distributions of more than 100 legal and illegal drugs such as narcotic drugs, opioids, antidepressants, antipsychotics, benzodiazepines, and major metabolites detected in authentic Caucasian hair samples in our laboratory are summarized. Depending on availability, the proximal sections of 1-6 cm in length were analyzed by liquid chromatography/tandem mass spectrometry following extraction of the finely chopped specimens by ultrasound in methanol. The data may present a helpful basis also for other laboratories for an initial evaluation of their results. However, these statistical data should not be used uncritically without including the circumstances of the particular case and the analytical procedures used. In addition, each laboratory in charge of interpreting results from hair analysis should balance own results as far as available with this data base.

Evaluation of the Safety of Drugs and Biological Products Used During Lactation: Workshop Summary.

This report serves as a summary of a 2-day public workshop sponsored by the US Food and Drug Administration (FDA) to discuss the safety of drugs and biological products used during lactation. The aim of the workshop was to provide a forum to discuss the collection of data to inform the potential risks to breastfed infants with maternal use of medications during lactation. Discussions included the review of current approaches to collect data on medications used during lactation, and the considerations for future approaches to design and guide clinical lactation studies. This workshop is part of continuing efforts to raise the awareness of the public for women who choose to breastfeed their infants.

[The Subretinal Implant - Clinical Results]. / Das subretinale Implantat ­ klinische Ergebnisse.

Since the end of the last century, subretinal electronic chips have been used to restore vision in patients blinded by degenerative retinal diseases such as retinitis pigmentosa. Various procedures have been suggested by different international scientific groups. The promising were the retinal-based concepts, for which there are now human data. The two distinct retina-based concepts not only differ in the site of stimulation (epi- or subretinal), but in their physiological concept. Whereas in camera-based systems (epiretinal, transchoroidal), eye movements cannot be used to detect objects, this is possible with subretinal access. It is as yet unclear as to whether this is relevant to restoring some kind of useful visual perception. This and other questions can only be answered by carefully designed human studies with sufficient patient numbers. Comparison of the visual results of the different groups is neither simple nor trivial. The implantations in each project need well trained and skilled retinal surgeons.

[Anti VEGF Therapy Under Real-Life Conditions: Adherance Determines Long Term Outcome in Neovascular AMD]. / Real-Life-Daten zur Anti-VEGF-Therapie: Therapieadhärenz bestimmt den Visuserhalt bei neovaskulärer AMD.

BACKGROUND: Data from real-life studies on neovascular AMD (nvAMD) generally fall significantly behind respective data from interventional prospective trials. This can be attributed at least partially to differences in patient cohorts concerning both stages of AMD (including consecutive scarring or atrophy), as well as adherence to therapy. We have been interested in the question which of the two factors most affects outcome in a real-life setting. PATIENTS AND METHODS: Retrospective study of 1500 cases of nvAMD over a time period of up to 5 years. Inclusion of all cases treated for nvAMD which received at least 3 intravitreal injections, no exclusion of cases. Treatment was according to pro re nata (PRN) scheme. RESULTS: In total, results for gain in visual acuity (letter score + 1,4 and - 0,8 for year 1 and 2, respectively), and number of injections (5,2 and 3,3) are well comparable to data from other German real-life studies. The variance within the dataset, however, is relatively large. Definition of one subgroup characterized by significantly better baseline visual acuity and significantly higher number of injections demonstrates expectedly significantly better outcome. This better performance, however, is outranged by a subgroup defined only by its significantly higher adherence to therapy. In fact, only approx. 30 % of all cases fall into this category and followed the desired PRN intervals reasonably well. This group shows gain in visual acuity of + 3,3 and + 1,6 with number of injections of 7,0 and 5,8 while not being selected according to stages of AMD at baseline. CONCLUSION: In this setting adherence to treatment more than the stage of nvAMD at baseline determined long term outcome of anti-VEGF treatment. This is encouraging for every days work where unfortunately late stages of AMD are not seen rarely. This finding emphases the importance of patient counseling and information to improve adherence to treatment.

Predictors for postoperative nausea and vomiting after xenon-based anaesthesia.

BACKGROUND: In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia. METHODS: With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication. RESULTS: Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59). CONCLUSIONS: The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia. CLINICAL TRIAL REGISTRATION: German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER.

First detection of ethylphenidate in human fatalities after ethylphenidate intake.

Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as "research chemical" via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription "ethylphenidate". An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia. At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively. Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110ng/mL, for liver 180ng/g, for pericardium fluid 131ng/mL, for urine 987ng/mL and for stomach content 20.7ng/mL, respectively. The stomach contained 200mL of a brownish-coloured liquid, resulting in a total amount of 4000ng ethylphenidate. The lowest calibrator for whole blood and serum was 1ng/mL and for urine 10ng/mL. As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmia) and might therefore have contributed to death, which was attributed to endocarditis in combination with pneumonia.

[Hematoma of the eye: there's more to this than meets the eye!]. / Blaues Auge: Was steckt dahinter?

A 3 1/2-year-old boy accidentally rode a bike into a shrubbery 1 day before he was presented at the clinic. He exhibited a hematoma of the right eyelid with ptosis without any obvious further injuries or visual complaints; however, a detailed examination revealed a profound loss of visual acuity of the right eye resulting from a serious traumatic optic neuropathy after being accidentally pierced by a twig through the left nostril.

[What can blind patients see in daily life with the subretinal Alpha IMS implant? Current overview from the clinical trial in Tübingen]. / Was können blinde Patienten mit dem subretinalen Alpha-IMS-Implantat im Alltag sehen? Aktuelle Übersicht aus der Tübinger klinischen Studie.

The subretinal visual implant is a scientific research approach to restore partial vision in end-stage hereditary retinal diseases by replacing the function of the degenerated photoreceptors by microelectronic chips. In a clinical trial in Tübingen these implants were tested on voluntary blind patients. By using the implants in daily living the patients reported valuable visual information. The subretinal microchip mediates subjectively useful visual information in near as well as in distant vision.

Evaluation of two immunoassay procedures for drug testing in hair samples.

A preliminary initial enzyme-linked immunosorbent assay (LUCIO-Direct ELISA kit) and a preliminary DRI enzyme immunoassay were evaluated for drug detection in head hair with respect to lowered cutoff values recommended in Germany for the control of abstinence in cases of re-granting of drivers' licences. Following drug classes were included: cannabinoids, opiates, cocaine like substances, amphetamine, methamphetamine (and methylenedioxyamphetamines), methadone, and benzodiazepines. 759 analyses were performed using LUCIO-Direct ELISA kits and 936 analyses using DRI enzyme immunoassay tests. Sample size for each drug group and immunoassay test reached from 74 to 178. The LUCIO-Direct ELISA kit revealed a sensitivity of 91% for amphetamine up to 98% for methadone (methamphetamine 92%, cocaine 94%, opiates 94%, benzodiazepines 96%) and values of specificity of 72% for methadone up to 89% for amphetamine and benzodiazepines. The test was not useful for a preliminary screening for tetrahydrocannabinol (sensitivity of 65%) in consideration of a suggested cutoff of 0.02 ng/mg. The DRI enzyme immunoassay test was only useful for morphine and cocaine testing at low recommended new cutoff values (0.1 ng/mg) revealing sensitivities of 94% and 99%, respectively.

Practical experiences in application of hair fatty acid ethyl esters and ethyl glucuronide for detection of chronic alcohol abuse in forensic cases.

This article presents results from 1872 hair samples, which were analyzed for fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG). The results were evaluated in the context of self-reported drinking behavior, the use of hair cosmetics, the gender of the sample donors and hair sample length. For comparison, CDT and GGT in serum were available in 477 and 454 cases, respectively. A number of alcohol abstainers or low moderate drinkers and excessive drinkers were selected for assessment of cut-offs for FAEEs in the proximal 6cm hair segments and for EtG in the proximal 3cm hair segments. Cut-off values were assessed by ROC analysis. It was found that the cut-offs of 1.0ng/mg FAEE and 30pg/mg EtG presently used for excessive drinking lead to a low portion of false positives (4% and 3% respectively) but to a higher portion of false negatives (23% and 25% respectively). Comparison of the mean and medium concentrations in samples without any reported hair cosmetics (N=1079) and in samples with reported use of hair spray (N=79) showed an increase by the factor of about two for FAEE but no significant difference for EtG. Mean values of EtG were decreased by 80% in bleached samples (N=164) and by 63% in dyed samples (N=96). There was no significant effect of bleaching and dyeing on FAEE. Hair gel and hair wax, oil or grease showed no significant effect on both FAEE and EtG. With respect to gender and investigated hair length ambiguous results were obtained because of major differences in the compared subpopulations of male with higher alcohol consumption and mainly shorter hair, and less drinking female with longer hair. For excessive drinkers FAEEs in the 0-6cm hair segment and EtG in the 0-3cm segment decreased with increasing time of reported abstinence before sample collection. These drinkers attain the level of teetotalers only after more than 10 months of abstinence. In comparison to scalp hair, FAEEs recovered from armpit hair and leg hair were lower and from chest hair were higher. EtG in armpit hair was lower and in leg hair higher than in scalp hair. It is concluded that the combined use of FAEE and EtG essentially increases the accuracy of interpretation since both markers complement each other by a different sensitivity to sources of error.

A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia.

The constantly recurring epistaxis means a great reduction of quality of life for patients with hereditary haemorrhagic telangiectasia (HHT). As yet, an ideal treatment has not been found. Vascular endothelial growth factor (VEGF) has been described as a possible new therapy. In particular, the success of submucosal doses <100 mg has not been analysed before. We injected bevacizumab (Avastin) submucosally in addition to Nd:YAG laser therapy. Doses <7.5 mg were used. To investigate the effect of these additional injections in comparison to laser therapy alone, a retrospective analysis was done. For this purpose a standardized patient questionnaire was completed, which included recording the patients' Epistaxis Severity Score (ESS) before and after the antibody treatment. Besides, patient files were analysed to collect objective data like haemoglobin levels and the number of blood transfusions needed. Data for eleven patients could be analysed. A significant improvement in the ESS resulting from additional bevacizumab therapy was observed (p < 0.01). In particular, the frequency of epistaxis (p = 0.011), duration of epistaxis (p < 0.01), severity of epistaxis (p < 0.01) and the need for acute medical treatment (p = 0.014) decreased significantly. The haemoglobin levels increased significantly (p = 0.011) and the number of blood transfusions declined. There were no side effects caused by the antibody treatment. Additional injections of a low dose of bevacizumab seem to be superior to Nd:YAG laser therapy alone. These results justify further studies.

The conditioning lesion effect on sympathetic neurite outgrowth is dependent on gp130 cytokines.

Sympathetic neurons, like sensory neurons, increase neurite outgrowth after a conditioning lesion. Studies in leukemia inhibitory factor (LIF) knockout animals showed that the conditioning lesion effect in sensory neurons is dependent in part on this cytokine; however, similar studies on sympathetic neurons revealed no such effect. Comparable studies with sensory neurons taken from mice lacking the related cytokine interleukin-6 (IL-6) have yielded conflicting results. LIF and IL-6 belong to a family of cytokines known as the gp130 family because they act on receptors containing the subunit gp130. In sympathetic ganglia, axotomy leads to increases in mRNA for four of these cytokines (LIF, IL-6, IL-11, and oncostatin M). To test the role of this family of cytokines as a whole in the conditioning lesion response in sympathetic neurons, mice in which gp130 was selectively eliminated in noradrenergic neurons were studied. The postganglionic axons of the SCG were transected, and 7days later the ganglia were removed and neurite outgrowth was measured in explant and dissociated cell cultures. In both systems, neurons from wild type animals showed enhanced growth after a conditioning lesion. In contrast, no enhancement occurred in neurons from mutant animals. This lack of stimulation of outgrowth occurred despite an increase in expression of activating transcription factor 3 (ATF3) in the mutant mice. These studies demonstrate that stimulation of enhanced growth of sympathetic neurons after a conditioning lesion is dependent on gp130 cytokine signaling and is blocked in the absence of signaling by these cytokines in spite of an increase in ATF3.

Long-term evaluation of anatomic and functional results after complicated retinal detachment treated with pars plana vitrectomy and heavy silicone oil tamponade.

BACKGROUND: Heavier than water tamponades offer the possibility to support the inferior part of the fundus after retinal detachment. The aim of this study was to evaluate the anatomic and functional outcome of complicated retinal detachment treated with vitreous surgery and heavy silicone oil (HSO) tamponade. Surgery was performed in eyes with rhegmatogenous retinal detachment (RD) predominantly in the lower hemisphere or with penetrating injury (either as primary intervention or after development of proliferative vitreoretinopathy [PVR]). MATERIALS AND METHODS: Sixty-one eyes of 61 patients with RD - mostly complicated by PVR - and a minimum follow-up of 12 months were included in this study. Vitreoretinal surgery with HSO (Oxane HD) tamponade was performed in all patients. In 52 patients, heavy silicone oil was used in the management of complicated RD. 9 patients had surgery for complicated RD after penetrating eye injury.The mean follow-up period was 30.3 +/- 10.2 months. RESULTS: The overall final anatomic success rate was 79 %. In 39 % of the cases the retina remained attached during the entire follow-up period. CONCLUSIONS: The anatomic success rate after surgery with HSO (Oxane HD) was relatively low; however, only complex cases bearing a higher risk of retinal re-detachment received HSO in this study. Oxane HD does not appear to have major advantages compared to conventional silicone oil or other new-generation heavy silicone oils in these cases.

Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients.

BACKGROUND: Due to low energy levels in microphotodiode-based subretinal visual prostheses, an external power supply is mandatory. We report on the surgical feasibility and the functional outcome of the extraocular part of an approach to connect a subretinal prosthesis to an extracorporeal connector in the retro-auricular space via a trans-scleral, transchoroidal cable. METHODS: Seven volunteers with retinitis pigmentosa received an active subretinal implant; energy was supplied by gold wires on a trans-sclerally, transchoroidally implanted polyimide foil leading to the lateral orbital rim where it was fixated and connected to a silicone cable. The cable was implanted subperiostally beneath the temporal muscle using a trocar to the retro-auricular space where it penetrated the skin for connection to a stimulator. To avoid subretinal movement of the implant, three tension relief points have been introduced. RESULTS: All implantations were performed as planned without complications, and no serious adverse events occurred in the postoperative period. Fixation of the implants was stable throughout the entire study duration of 4 weeks; permanent skin penetration proved to be uncomplicated. Motility was minimally restricted in downgaze and ab-/adduction. Explantation was uneventful. CONCLUSION: The above-described procedure provides a method for stable fixation of a subretinal device with a trans-scleral, transchoroidal cable connection to an extracorporeal connector.

[Cost calculations for treating penetrating eye injuries within the DRG C01Z at a university eye hospital]. / Kostenkalkulation für die Behandlung von offenen Augenverletzungen in der DRG C01Z an einer Universitäts-Augenklinik.

BACKGROUND: Since 2004, inpatient health care for penetrating eye injuries in Germany had been paid according to the calculated DRG C01Z. Because the extent of treatment mainly derives from the extent of eye damage, this DRG economically summarises very heterogeneous cases. It was the aim to check the cost recovery for the surgical treatment of penetrating eye injuries at a university eye hospital. MATERIAL AND METHODS: Performance data for the DRG C01Z were collected for the years 2005 and 2006 using the E1 sheets according to section sign21 KHEntG. Costs for single operations were calculated from fixed and variable costs for the operating theatre and the ward, including costs for personnel and supplies. RESULTS: In the 2-year period, out of 4,721 inpatient procedures, 180 perforating eye injuries were surgically treated. In 80 cases, a pure corneal/scleral suture (plus cataract surgery, n=10; mean operating time 67.81 min) was performed. In the other 100 cases, a pars plana vitrectomy (ppV) with adjuvant measures (mean operating time 124.69 min) was needed. Each operation had fixed surgical costs of EUR 130.60; variable costs, including personnel and supplies, varied between EUR 570 for corneal/scleral suture (+/-EUR 250 for combined cataract surgery (n=10) and EUR 1230 (mean) for a ppV. Cost-effective additional adjuncts such as cerclage, perfluorocarbon, gas, silicone oil, or cataract surgery led to extra costs of between EUR 51 and EUR 250 per adjunct (mean EUR 182). At least two of these adjuncts were used in 50% of ppVs, and at least one was used in 90% of ppVs. Hospitalisation costs were about EUR 2184 (EUR 273 per day), with a mean stay of 8 days. The overall costs of an operation for penetrating eye injuries differed significantly in terms of the procedure (corneal/scleral suture: EUR 2662, mean length of stay 7.06 days; ppV: EUR 3712, mean length of stay 8.62 days). Additional costs for multiple surgeries, as occurred in 11.1% of all cases, were not compensated by the DRG system. CONCLUSION: In consideration of a relative DRG weight of 1,177 and a base rate of EUR 2723.79 in Bavaria for 2005 and 2006, perforating eye injuries were compensated within the C01Z DRG at EUR 3205,96. Thus, for ppVs no costs are recovered, whereas "pure suture" procedures are overweighted. Due to this inhomogeneity, a split in the C01Z DRG is necessary.

Application of discriminant analysis to differentiate between incorporation of cocaine and its congeners into hair and contamination.

The requirement to differentiate between incorporation and external contamination of drugs into hair is undisputed, in particular when dealing with compounds which are administered by sniffing or inhalation (e.g. cocaine). With the aim of making this discrimination, hair samples from cocaine (COC) users (group IN) and seized cocaine samples (group OUT) were compared regarding the parameters benzoylecgonine (BZE), ecgonine methyl ester (EME), ecgonine (ECG), anhydroecgonine methyl ester (AEME), cocaethylene (CE) and norcocaine (NCOC). Since most of these compounds may be minor by-products of COC or be formed by biotransformation or chemical degradation, the stability of each substance was carefully examined. COC was found to be converted into significant amounts of BZE, EME and ECG even under mild extraction conditions, while traces of NCOC proved to be a ubiquitous by-product of COC. Cocaine positive hairs and seized cocaine samples (diluted to relevant concentrations) were equally preprocessed and analyzed by LC-MS-MS. Out of the metabolites listed above, NCOC, CE and AEME (each normalised to COC) were significantly increased in the incorporation group (i.e. hair samples from cocaine users). Based on this approach, a statistical discriminant analysis enabled us to make a prediction (and estimation of uncertainty) for each cocaine positive hair sample as to its likelihood of belonging to the group of cocaine users or of being contaminated.

Activating transcription factor 3 induction in sympathetic neurons after axotomy: response to decreased neurotrophin availability.

Activating transcription factor 3 (ATF3) is induced in a high proportion of axotomized sensory and motor neurons after sciatic nerve transection. In the present study, we looked at the expression of this factor in the superior cervical ganglion (SCG) after axotomy and after other manipulations that induce certain aspects of the cell body response to axotomy. Sympathetic ganglia from intact rats and mice exhibit only a very occasional neuronal nucleus with activating transcription factor 3-like immunoreactivity (ATF3-IR); however, as early as 6 h and as late as 3 weeks postaxotomy, many of the neurons showed intense ATF3-IR. A second population of cells had smaller and generally less intensely stained nuclei, and at least some of these cells were satellite cells. Lesions distal to the SCG induced by administration of 6-hydroxydopamine or unilateral removal of the salivary glands produced increases in ATF3-IR similar to those seen after proximal axotomy, indicating that this response is not strictly dependent on the distance of the lesion from the cell body. Two proposed signals for triggering ATF3 expression were examined: reduction in nerve growth factor (NGF) availability and induction of the cytokine leukemia inhibitory factor (LIF). While administration of an antiserum raised against NGF to intact animals induced ATF3-IR, induction of ATF3-IR after axotomy was not reduced in LIF null mutant mice. Since axotomy, 6-hydroxydopamine, and sialectomy are known to decrease the concentration of NGF in the SCG, our data suggest that these decreases in NGF lead to increases in ATF3-IR. Furthermore, since the number of neurons in the SCG expressing ATF3-IR was greater after axotomy than after antiserum against NGF treatment, this raises the possibility that decreased NGF is not the only process regulating ATF3 expression after axotomy.

[Pleomorphic malignant fibrous histiocytoma of the periorbital region]. / Pleomorphes malignes fibröses Histiozytom der Periorbitalregion.

BACKGROUND: Pleomorphic malignant fibrous histiocytomas (undifferentiated pleomorphic sarcomas) belong to the soft tissue tumours and are more likely in elder patients. About 3 % percent of all pleomorphic malignant fibrous histiocytomas arise in the head and neck region. 30 % of these histiocytomas develop in the paranasal sinuses. Occurrence in the periorbital region is a very rare event. In spite of their pleomorphic pattern the treatment is solely surgical excision. Haematogenic or loco-regional lymphogenic metastases are very rare. PATIENT: A 91 year old female patient presented because of a prominent tumour in the upper right periorbital region. As stated in the case history, the tumour had developed within the previous 6 months. The tumour measured about 3 x 4 cm. It was tight to resiliant and seemed to not be adherent to the underlying structures. Pain or hypesthaesia were not existent. Due to the mass of the tumour a ptosis was present. Additionally, there was a mechanical lack in the movement of the eyeball in the upper direction. The papilla was vital and differentiated. Visual acuity was decreased due to a mature cataract. CLINIC: Neither CT nor MRI could give a clue to the tumour entity. Infiltration of the periorbital structures or the eyeball could not be ruled out. A biopsy was classified as a malignant fibrous tumour with the subclassification of an atypical fibroxanthoma. The final histopathological classification after total excision of the tumour showed perineural growth and angioinvasion. Therefore the tumour classification was changed to pleomorphic malignant fibrous histiocytoma (undifferentiated pleomorphic sarcoma). The defect was closed with a full skin graft on the basis of a galea periosteal flap. CONCLUSION: The histopathological examination could not provide the correct diagnosis initially. Immunohistochemical stainings (Vimentin) were carried out to characterise the tumour. This underlines that even with state of the art procedures the classification of neoplasias can be very difficult. In the process of finding the right diagnosis sometimes a change from benign to malignant occurs and alters the treatment regime.