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Purpose Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

Summary Background Patient safety is a central issue of health care provision. There are various approaches geared towards improving health care provision and patient safety. By conducting a systematic retrospective error analysis, the present article aims to identify the most common complaints brought forth within the field of dermatology over a period of ten years. Methods The reports of the Expert Committee for Medical Malpractice Claims of the North Rhine Medical Association (from 2004 to 2013) on dermatological procedures were analyzed (n = 247 reports in the field of dermatology). Results Expert medical assessments in the field of dermatology are most frequently commissioned for nonsurgical therapies (e.g. laser therapy, phototherapy). While suspected diagnostic errors constitute the second most common reason for complaints, presumed dermatosurgery-related errors represent the least common reason for commissioning expert medical assessments. Conclusions The most common and easily avoidable sources of medical errors include failure to take a biopsy despite suspicious clinical findings, or incorrect clinicopathological correlations resulting in deleterious effects for the patient. Furthermore, given the potential for incorrect indications and the inadequate selection of devices to be used as well as their parameter settings, laser and phototherapies harbor an increased risk in the treatment of dermatological patients. The fourth major source of error leading to complaints relates to incorrect indications as well as incorrect dosage and administration of drugs. Analysis of expert medical assessment reports on treatment errors in dermatology as well as other medical specialties is helpful and provides an opportunity to identify common sources of error and error-prone structures.

Zusammenfassung Hintergrund Patientensicherheit ist ein zentraler Inhalt der Gesundheitsversorgung. Zur Verbesserung der Gesundheitsversorgung und der Patientensicherheit gibt es verschiedene Ansatze. Die vorliegende Arbeit hat das Ziel, mit Hilfe einer systematischen retrospektiven Fehleranalyse die haufigsten Beanstandungen innerhalb des Fachbereiches Dermatologie in einem Zeitraum von zehn Jahren zu identifizieren. Methodik Die Gutachten der Gutachterkommission fur arztliche Behandlungsfehler bei der Arztekammer Nordrhein zu Verfahren in der Dermatologie aus dem Zeitraum zwischen 2004 und 2013 wurden ausgewertet (n = 247 Gutachten im Fachgebiet Dermatologie). Ergebnisse Gutachtenanforderungen zur Prufung vermeintlicher Behandlungsfehler erfolgen in der Dermatologie am haufigsten aufgrund nichtoperativer Therapien (z. B. Lasertherapie, Lichttherapie). Vermutete Diagnosefehler sind der zweithaufigste Grund fur Gutachtenanforderungen. Am seltensten kommt es zu Gutachtenanforderungen wegen vermuteter Fehler durch dermatologische Operationen. Schlussfolgerungen Die haufigsten, einfach zu vermeidenden Fehlerquellen umfassen nicht durchgefuhrte Biopsien trotz verdachtiger klinischer Befunde oder unkorrekte klinisch-histopathologische Korrelationen, die zum Schaden des Patienten fuhrten. Weiterhin bergen Lasertherapien und Lichttherapien aufgrund falscher Indikationen, Geratewahl oder Parametereinstellung erhohte Risiken bei der Behandlung dermatologischer Patienten. Als vierte Hauptfehlerquelle kommt eine falsche Indikationsstellung, Dosierung und Applikation bei der Medikation hinzu. Die Analyse medizinischer Gutachten zu Behandlungsfehlern in der Dermatologie aber auch anderer Fachrichtungen ist hilfreich und eine Moglichkeit, um haufige Fehlerquellen und eventuell fehleranfallige Strukturen zu identifizieren.

Patient safety is a central issue of health care provision. There are various approaches geared towards improving health care provision and patient safety. By conducting a systematic retrospective error analysis, the present article aims to identify the most common complaints brought forth within the field of dermatology over a period of ten years.The reports of the Expert Committee for Medical Malpractice Claims of the North Rhine Medical Association (from 2004 to 2013) on dermatological procedures were analyzed (n = 247 reports in the field of dermatology).Expert medical assessments in the field of dermatology are most frequently commissioned for nonsurgical therapies (e.g. laser therapy, phototherapy). While suspected diagnostic errors constitute the second most common reason for complaints, presumed dermatosurgery-related errors represent the least common reason for commissioning expert medical assessments.The most common and easily avoidable sources of medical errors include failure to take a biopsy despite suspicious clinical findings, or incorrect clinicopathological correlations resulting in deleterious effects for the patient. Furthermore, given the potential for incorrect indications and the inadequate selection of devices to be used as well as their parameter settings, laser and phototherapies harbor an increased risk in the treatment of dermatological patients. The fourth major source of error leading to complaints relates to incorrect indications as well as incorrect dosage and administration of drugs. Analysis of expert medical assessment reports on treatment errors in dermatology as well as other medical specialties is helpful and provides an opportunity to identify common sources of error and error-prone structures.

Lichen planus pemphigoides is an autoimmune subepidermal blistering disease. The finding of immunoglobulin G antibodies directed against the basement membrane zone differentiates it from bullous lichen planus. The aim of this study was to identify the target antigen of lichen planus pemphigoides autoantibodies. Sera from lichen planus pemphigoides patients (n = 4) stained the epidermal side of NaCl-split human skin in a pattern indistinguishable from that produced by bullous pemphigoid sera. In bullous pemphigoid, the autoimmune response is directed against BP180, a hemidesmosomal transmembrane collagenous glycoprotein. We previously demonstrated that bullous pemphigoid sera predominantly react with a set of four epitopes (MCW-0 through MCW-3) clustered within a 45 amino acid stretch of the major noncollagenous extracellular domain (NC16A) of BP180. By immunoblotting and enzyme-linked immunosorbent assay, lichen planus pemphigoides sera were also strongly reactive with recombinant bullous pemphigoid 180 NC16A. The lichen planus pemphigoides epitopes were further mapped using a series of overlapping recombinant segments of the NC16A domain. All lichen planus pemphigoides sera reacted with amino acids 46-59 of domain NC16A, a protein segment that was previously shown to be unreactive with bullous pemphigoid sera. Two lichen planus pemphigoides sera, in addition, reacted with the immunodominant antigenic region associated with bullous pemphigoid. In conclusion, there are now five bullous diseases that are associated with an autoimmune response to BP180: bullous pemphigoid; pemphigoid/herpes gestationis; cicatricial pemphigoid; linear immunoglobulin A disease; and lichen planus pemphigoides. In addition, we have identified a novel epitope within the BP180 NC16A domain, designated MCW-4, that appears to be uniquely recognized by sera from patients with lichen planus pemphigoides.

Eosinophilic globules are commonly found in Spitz nevi and can be of help in the differential diagnosis with melanoma. Despite their use as a diagnostic marker, there are conflicting concepts concerning the mechanism of the formation of these globules. Because pyknotic nuclei are often present in the cells surrounding the globules, many believe that apoptotic cell death of keratinocytes and melanocytes is an important mechanism in their formation. We studied nine Spitz nevi containing 21 eosinophilic globules for apoptotic cell death around and within Kamino bodies using the TUNEL method (TdT-mediated dUTP-x nick end-labeling method). In none of the cases were positive cells seen in the vicinity of the globules. Single apoptotic cells were found only sporadically in the melanocytes of the neoplasms (one to four per section) and were scattered throughout the entire lesion. The absence of apoptosis-specific labeled cells in the vicinity of eosinophilic globules and the rare occurrence of positive stained cells in other parts of the tumors makes apoptotic cell death unlikely to be relevant in the formation of eosinophilic globules.

Progressive nodular histiocytosis (PNH) represents a very rare type of non-Langerhans cell histiocytosis (NLCH). It can be distinguished from other types by the occurrence of yellow to red-brown papules and nodules measuring a few centimeters in size. Histologically the nodules represent spindle-cell xanthogranulomas. We report on two new cases of PNH with novel clinical symptoms. In the first case, the patient had microcytic anemia due to massive iron deposition in the nodules and a progressively worsening limp due to involvement of the soles. The complex therapeutic challenge was effectively managed by successive surgical ablation of all visible lesions. The second patient had epibulbar infiltrates. The clinical variability of PNH leads to considerable overlap with other forms of NLCH.

Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as 'favor benign' (A-) or 'favor malignant' (A+). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas.

Background Anti-laminin 5 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the major basement membrane component laminin 5 (laminin 332, epiligrin). Objective and Methods We reviewed 17 biopsy specimens from 9 patients with anti-laminin 5 MMP in an attempt to define typical histopathologic features of the disease. Results Fifteen specimens showed subepidermal blister formation, while two biopsy specimens revealed an epithelial ulcer. In 11 biopsies a sparse to moderate inflammatory infiltrate composed of lymphocytes and neutrophils with some eosinophils was observed. Four biopsies showed a dense infiltrate dominated by neutrophils in two cases and by eosinophils in one case. The remaining biopsy revealed a dense lymphoplasmacellular infiltrate without granulocytes. Scarring of the upper dermis was present only in 5 specimens. Immunohistochemical analysis localized type IV collagen to the dermal side of the blister, suggesting that split formation occurred within the lamina lucida of the cutaneous basement membrane. Limitations The number of patients studied was relatively small. Conclusions Histopathology of anti-laminin 5 MMP is characterized by subepidermal blistering and a sparse to moderate superficial lymphohistiocytic infiltrate with neutrophils and/or eosinophils. Both infiltrate density and composition may vary, making anti-laminin 5 MMP indistinguishable from other autoimmune subepidermal blistering diseases by histopathology alone. Scarring is present only in a minority of cases and is not a sensitive clue to the diagnosis of anti-laminin 5 MMP.

A 45-year-old woman presented with recent onset of left-sided chest pain. On clinical examination, these symptoms seemed to be strictly localized to a region that was marked by a long-standing cutaneous erythematous lesion. Laboratory results showed no gross abnormalities. Radiological imaging including conventional X-ray, MRI scans, and 3D CT reconstruction of the rib cage revealed circumscript destruction of the left lateral ribs 9-11. Histological analysis of a rib biopsy showed angiomatous hypervascularization and intracortical fibrosis. In keeping with these findings, the patient's condition was diagnosed as Gorham-Stout disease, a rare condition with localized, often unilateral, bone destruction. Monotherapy with bisphosphonates (pamidronate 30 mg i.v. every 3 months) was initiated, leading to rapid disappearance of local pain. Follow-up over 24 months documented a stable clinical and radiological picture without evidence of progressive bone destruction.

We describe a 76-year-old white woman with a 6-month history of intensive pruritus and excoriated papules resembling subacute prurigo. Histopathology showed signs of chronic dermatitis, whereas findings by direct and indirect immunofluorescence microscopy were compatible with bullous pemphigoid (BP). The patient's serum contained IgG autoantibodies that recognized epitopes on both BP180 and BP230 by Western blot analysis of epidermal extracts. In addition, we found strong reactivity with recombinant NC16A, an immunodominant region of BP180 targeted in the majority of BP sera, whereas no antibodies against the keratinocyte-derived soluble BP180 ectodomain (LAD-1) or the recombinant intracellular domain of BP180 were detected. The patient's disease responded well to oral methylprednisolone and mycophenolate mofetil. Disease activity correlated with enzyme-linked immunosorbent assay reactivity of antibodies to BP180 but not with titers of antibodies to the dermoepidermal junction as determined by indirect immunofluorescence on salt-split skin. Our findings suggest that the subacute prurigo form of BP is a true variant of BP. (J Am Acad Dermatol 2002;47:133-6.)

Spitz nevus is a benign neoplasm of melanocytes that can be difficult or impossible to distinguish from melanoma by clinical and histopathologic examination. We studied genomic DNA from 17 Spitz nevi by comparative genomic hybridization (CGH). Thirteen lesions showed no chromosomal aberrations, three cases had a gain involving the entire p-arm of chromosome 11, and one case showed a gain of chromosome 7q21-qter. Fluorescence in situ hybridization (FISH) on lesional tissue with a probe for the p-arm of chromosome 11 showed 6–10 p-arm signals per nucleus in those cases with a CGH-detected gain of chromosome 11p. One case with a normal CGH profile also showed increased copy number of 11p by FISH. Thus, the majority of Spitz nevi have a normal chromosomal complement at the level of CGH resolution; however some may contain gains, with 11p apparently being the most frequently involved location. These findings differ significantly from the previously reported changes in primary cutaneous melanoma, which show frequent deletions of chromosomes 9p (82%), 10q (63%), 6q (28%), and 8p (22%), as well as gains of chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%) by CGH analysis. These clear differences in the location and frequencies of chromosomal aberrations in Spitz nevi and primary cutaneous melanomas could represent a basis for developing adjunctive techniques for refining accuracy in the difficult differential diagnosis of spitzoid melanocytic neoplasms.

The molecular and structural analysis of cells within their tissue context helps us understand disease mechanisms, such as carcinogenesis. Standard analysis of cutting specimens into thin (4 micrometer) sections, followed by labeling and visual microscopic analysis, has the limitation that tissue properties can only be studied within the section plane, and not perpendicular to the plane. We solved these limitations by building a system for registering images of adjacent sections. In addition, the system enables analysis of many molecular markers in a specific tissue volume, by labeling different sections with different markers, followed by using the system to locate the relevant tissue volume in each section. The system has three stages. First, it automatically images each entire section and two fiducial markers per slide. After this stage, the slides can be removed from the microscope. In stage two, pairs of images of adjacent sections are registered. This is done by interactively marking several points that are common to both images, which are used to calculate the translation and rotation of the images relative to each other. Different registrations can be performed on different parts of the images to account for differential stretching, tearing and folding of sections. In stage three, a slide is placed on the microscope stage and the analyst can bring a specific location into the field of view by referring to it in the previously acquired image. Accuracy is approximately equal to 10 micrometers.