Search

Background and Objectives: Primary cutaneous diffuse large B-cell lymphoma, NOS (PCLBCL/NOS) is a rare PCLBCL. Only few data are available for this tumor. The aim of this study was to identify clinical and/or immunohistochemical markers (in addition to Bcl-2) that characterize PCLBCL/NOS, assist in differentiating it from PCLBCL, leg type (PCLBCL/LT) and help to assess the clinical course/prognosis., Patients and Methods: Bcl-2 - PCLBCL/NOS) cases (n = 14 were compared with Bcl-2 + PCLBCL/LT cases (n = 29)., Results: PCLBCL/NOS patients were younger, predominantly male and had better survival rates than patients with PCLBCL/LT. Patients with PCLBCL/NOS presented more often with larger plaques limited to one or two contiguous body regions, whereas PCLBCL/LT cases often presented with disseminated lesions. Neoplastic cells had a higher proliferation rate (Ki67) in PCLBCL/LT patients. The tumor microenvironment of PCLBCL/NOS had a more prominent CD3 + infiltrate. Overall survival data for the whole cohort (n = 37) revealed that female gender and Bcl-2 expression correlated with a worse survival rate. Bcl-6 expression and centroblastic subtype correlated with better outcomes. None of the other markers studied (e.g. GCB/non-GCB subtype) correlated with survival rate., Conclusions: PCLBCL/NOS and PCLBCL/LT differ in their clinical behavior and outcomes. Bcl-2 still seems to be the best marker for discriminating between these two subgroups. Bcl-2, female gender and Bcl-6 represent prognostic markers for PCLBCL., (© 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Hintergrund Und Ziele: Mittelschwere bis schwere Psoriasis erfordert häufig eine langfristige systemische Behandlung. Die Therapietreue bezüglich eines Medika-ments (Überlebensrate, "Drug Survival") reflektiert dessen Wirksamkeit, Sicherheit sowie die Zufriedenheit mit der Behandlung und ist ein Indikator für den Therapieerfolg. Das Ziel der vorliegenden Studie was die Ermittlung der "Drug-Survival"-Raten sowie der Gründe für den Abbruch einer Behandlung mit Fumarsäureestern (fumaric acid esters, FAE), Methotrexat (MTX), Acitretin (ACI), Cyclosporin A (CyA), Adalimumab (ADA), Etanercept (ETA), Infliximab (INF) und Ustekinumab (UST) bei Patienten mit mittelschwerer bis schwerer Psoriasis., Patienten Und Methoden: Wir führten eine retrospektive Analyse an 373 Patienten durch, die im Zeitraum 1/2003-5/2014 insgesamt 696 Behandlungen an einem deutschen Universitätsklinikum erhalten hatten., Ergebnisse: Die unbereinigte Überlebenswahrscheinlichkeit war für UST am höchsten, gefolgt von ADA, ETA, INF, FAE, MTX, ACI und CyA. In der multivariaten Regressionsanalyse mit FAE als Referenz betrug die Hazard Ratio (HR) für einen Abbruch 0,14 (95 % Konfidenzintervall: 0,06-0,35) bei UST, 0,43 (0,26-0,73) bei ADA, 2,11 (1,14-3,91) bei ACI und 3,26 (1,44-7,39) bei CyA. Das "Drug Survival" von INF war länger, wenn es in Kombination mit MTX eingesetzt wurde (HR 2,87; 1,21-6,81). Traditionelle systemische Antipsoriatika sowie INF wurden am häufigsten aufgrund von Nebenwirkungen abgesetzt; alle anderen Biologika aufgrund ihrer Unwirksamkeit für kutane Psoriasis-Läsionen. SCHLUSSFOLGERUNGEN: "Drug-Survival"-Raten sollten bei der Therapieentscheidung berücksichtigt werden, um den Patienten eine bestmögliche Langzeitstrategie zu bieten., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Background and Objectives: Moderate-to-severe psoriasis frequently requires long-term systemic therapy. Reflecting efficacy, safety, and treatment satisfaction, drug survival is an indicator of therapeutic success. The objective of the present study was to assess drug survival rates and reasons for discontinuation of fumaric acid esters (FAE), methotrexate (MTX), acitretin (ACI), cyclosporine A (CyA), adalimumab (ADA), etanercept (ETA), infliximab (INF), and ustekinumab (UST) in patients with moderate-to-severe psoriasis., Patients and Methods: We performed a retrospective analysis of 373 patients who had received a total of 696 treatment courses at a German university hospital in the period 1/2003-5/2014., Results: The crude probability of survival was highest for UST, followed by ADA, ETA, INF, FAE, MTX, ACI, and CyA. In multivariate regression analysis using FAE as reference, hazard ratios (HR) for discontinuation were 0.14 (95 % confidence interval: 0.06-0.35) for UST, 0.43 (0.26-0.73) for ADA, 2.11 (1.14-3.91) for ACI, and 3.26 (1.44-7.39) for CyA. INF showed longer survival when combined with MTX (HR 2.87, 1.21-6.81). Traditional systemic antipsoriatic agents as well as INF were most frequently discontinued due to adverse events; all other biologics, due to inefficacy with respect to cutaneous lesions., Conclusions: Drug survival rates should be integrated into therapeutic decisions in order to provide patients with an optimal long-term strategy., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Sézary syndrome, the leukemic variant of cutaneous T-cell lymphoma, is still an enigmatic disease with a fatal prognosis. Recent research, however, has identified a multitude of dysregulated molecular pathways that contribute to malignant transformation and therapy resistance of Sézary cells (SC). With respect to T-cell development, SC either represent naive T cells, T effector memory or T central memory cells. Functionally, SC may differentiate into Th2, Treg, or even Th17 cells. Despite their plasticity, SC express characteristic diagnostic marker proteins including CD158k, CD164, FcRL3, and PD-1 as well as skin-homing receptors such as CLA and CCR4. Already tested in (pre)clinical trials, CD158k, PD-1, CTLA-4, and CCR4 also represent promising therapeutic targets. Molecular alterations in SC include transcription factors such as STAT3, 4, and 5, as well as TWIST1 and TOX. TWIST1 induces expression of DNM3os containing the miR-199a2/214 cluster, a key hub controlling multiple cancer networks. In addition, activation of NFκB and the MAPK pathway as well as altered TCR signaling cause apoptosis resistance. Recently, whole genome and exome sequencing has revealed somatic copy number variations as predominant mutations in SC, primarily affecting apoptosis, NFκB signaling, DNA integrity, and T-cell activation. In order to facilitate development of novel therapies, improved in vivo models, which better reflect the pathogenesis and clinical course of Sézary syndrome, are currently being generated., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

The concept of a unidirectional cascade of metastatic events has been replaced in recent years by the metastatic cycle - the concept of a dynamic feed forward cycle of metastatic niches that evolve upon reciprocal interactions with the primary tumor and disseminating cancer cells. Primary tumors interact with pre-metastatic sites preparing organ-specific pre-metastatic niches. Metastasis-initiating cells home to and succumb to interactions with developing organ-specific metastatic niches, and secondary recirculating cancer cells interact back with the primary. Metastatic tropism as well as metastatic disease progression are a result of this feed forward cycle of dynamic, reciprocal interactions of cancer cells with their diverse metastatic niches. A better understanding of the multifaceted contributions of the organ-specific metastatic niches and their complex changes on cancer cell dissemination and of the mutual effects of the cellular and molecular mechanisms involved will open new avenues to better therapies for hitherto intractable progressive disease states of cancer patients and for adjuvant treatment options preventing relapses in tumor-free patients., (© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

The cardiovascular system is a circulatory system that transports the blood and reaches out to almost every site of the body. Endothelial cells (EC) as the innermost cell layer of blood vessels constitute a huge interface between the blood and nearly all other tissues and cells. Although blood vessels and their EC were considered as rather inert and passive conduits early in the history of vascular discoveries, progress in vascular research now suggests that EC are actively involved in a plethora of physiological or pathophysiological processes. Endothelial heterogeneity and the concept of vascular niches are in the spotlight of current research in vascular biology. Endothelial heterogeneity comprises morphologic, molecular and functional features. It allows EC to adapt to the organ- and site-specific requirements exhibited by different segments of the vascular tree. In organ-specific vascular niches, EC mutually interact with neighboring cells. EC-derived cytokines, called angiokines, acting in a paracrine (angiocrine) fashion have been shown to be decisively involved in various biological processes ranging from stem cell maintenance to organ regeneration as well as cancer progression and metastasis. In summary, EC should always be considered as teammates in the maintenance and regulation of complex multicellular network interactions in health and disease., (© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Background: Primary cutaneous CD30(+) anaplastic large cell lymphomas (C-ALCL) have indolent clinical behavior with an estimated 5-year survival rate of 95%. The clinical features and disease courses of C-ALCL identified in the lymphoma registry of Mannheim University hospital are described in the following., Patients and Methods: All C-ALCL patients identified in the database were analyzed in regard to clinical picture, histology, immunohistochemistry, molecular biology, staging, therapy, follow-up, and outcome., Results: 14 C-ALCL patients were identified. The mean age was 69 years and 57% were men. Solitary skin lesions in one anatomical region were seen in 12 patients upon initial diagnosis. Two patients presented with multiple lesions at different anatomical sites. In 2 patients there was specific lymph node involvement. In one C-ALCL patient, follow-up over 17 months revealed extracutaneous infiltration. Half of the patients relapsed and 36% had multiple episodes. The majority of our patients were treated with surgical excision followed by electron beam radiotherapy. The 5-year survival rate was 93% in C-ALCL., Conclusions: The clinical presentation of C-ALCL varies. Staging procedures and a close clinical pathological correlation at initial diagnosis are essential. Due to a high rate of relapses and the possibility of developing extranodal manifestations over the course of the disease, close follow-up is recommended., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: In Germany little data on the epidemiology and histology of lip cancers are available, as lip cancers are commonly pooled together with head and neck tumors., Patients and Methods: Retrospective analysis of 181 patients with malignant tumors of the lips with respect to gender, location, histology, risk factors and comorbidity., Results: There were 90 women and 91 men with a mean age of 71 years. 98 had a tumor on the upper lip and 83 patients on the lower lip. Tumors of the upper lip showed a slight female preference (61%). In contrast lower lip cancer was more common (64%) in men. Histological analysis revealed that in both regions nodular basal cell carcinomas as well as squamous cell carcinomas (NOS) are the most common subtypes. Vertical tumor thickness of squamous cell carcinomas was in most cases smaller than 6 mm (n = 71) and only in 4 cases was a tumor thickness of >6 mm detected. Altogether, 57% of the patients reported a high to very high sun exposure., Conclusions: In comparison to previous studies we found a weaker preference for women for tumors of the upper lip and also a weaker preference for men for tumors of the lower lip. The causes remain unclear, but could be causally related to an increased life expectancy and/or changed risk profile., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: Malignant melanoma (MM) is dramatically increasing in light-skinned populations worldwide. Staging and regular follow-up examinations are essential. The purpose of this study was to compare the diagnostic accuracy of whole-body MRI with the standard diagnostic algorithm (whole-body CT and brain MRI) in patients with stage III/IV MM., Patients and Methods: A group of 50 consecutively admitted patients with stage III/IV MM were included in the study. Whole-body CT and brain MRI scans were performed. Additionally, all patients underwent a whole-body MRI (1.5 Tesla Magnetom Avanto, Siemens Healthcare Sector, Erlangen). The findings were compared on a lesion-by-lesion basis as part of clinical routine follow-up., Results: 33 patients received a follow-up CT and were evaluated. Overall, 824 lesions were detected. The sensitivity of whole-body MRI was observer-dependent. MRI was slightly less sensitive than CT according to the findings of the two most experienced observers (73.4 % vs. 78.2 %, p = 0.0744). CT was significantly more sensitive in the detection of small (1-5 mm) pulmonary nodules (2.9 % vs. 66.9 %, p < 0.0001). Yet overall, MRI was significantly more specific than CT (83.4 % vs. 50.4 %, p < 0.0001)., Conclusions: Whole-body MRI in compliance with standard requirements for the observers (high level of experience) should be considered as an appropriate alternative to CT without ionizing radiation, particularly for young patients with advanced MM., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: Leeches were used for medical purposes as long as 2 000 years ago in ancient Egypt. In recent years the use of medicinal leeches became rather popular again, e. g. to improve blood circulation in ischemic tissue after reconstructive plastic surgery., Patients and Methods: In a single center, retrospective study 23 consecutive cases were analyzed in which medicinal leeches had been used therapeutically after plastic reconstructive surgery. All cases were categorized regarding the indication for leech therapy, the onset, the duration, the number of leeches and the number of sessions., Results: Among the group of patients there were 7 female and 16 male patients with a mean age of 73 ± 14 years (48-94 years) altogether. The main indications were venous congestion (12/23; 52 %) and hematoma (9/23; 39 %). Two cases were diagnosed with a necrosis of the tip of the flap and therefore received leech therapy (2/23; 9 %). The average number of leeches was 2.6 leeches/session, the number of sessions was 1.7 ± 0.8. 20/23 patients (87 %) showed a restitutio ad integrum after leech therapy, in 3/23 patients (13 %) a necrosis of the tip of the flap could not be prevented. A clinical improvement was noticed after an average of 1.1 ± 0.3 days., Conclusions: The early application of medicinal leeches can improve local hemodynamic conditions. Leech therapy is a simple and effective method; the cost efficiency of the treatment is high., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: Two stage reconstructions of deep scalp wounds with exposed calvarial bone require a vital granulation tissue. By evaluating different surgical approaches functional and cosmetic results as well as economic aspects have to be taken into account., Patients and Methods: 52 patients undergoing three different surgical procedures for soft tissue reconstruction of complex scalp wounds with exposed bone were included into a retrospective study. All patients underwent a two stage procedure with 3D histologic control, soft tissue reconstruction and final split thickness skin grafting. Soft tissue reconstruction was carried out using allogenic fascia lata, an artificial skin substitute or a negative pressure wound therapy (NPWT). The costs for all used materials as well as personnel and infrastructure were calculated., Results: Comparing the costs for the different treatments, the fascia lata group was least costly (4,475 €) followed by the artificial skin substitute group (4,557 €). The highest expenses occurred in the NPWT group (7,.521 €). The artificial skin substitute group had the fewest dressing changes and the shortest treatment time., Conclusions: Although dermal regeneration templates are expensive, their use may be economic. NPWT causes high treatment costs due to high daily rental rates and frequent and time-consuming dressing changes., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: Extracorporeal photopheresis (ECP) is recommended for the treatment of Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL). Several combination therapies are used to increase response rates to ECP., Patients and Methods: We report our experience with the combination therapy of ECP, interferon-alpha, PUVA and topical corticosteroids in SS., Results: The treatment outcome in 12 SS patients was retrospectively analyzed and showed an overall response rate to this combination treatment of 42 % with 4/12 patients achieving a partial remission and 1/12 patients a stable disease. The median overall survival time was 42 months. We investigated several clinical and laboratory parameters as an indicator for a response to treatment in our patient cohort. A combined analysis of the erythroderma assessment scale, WBC, LDH, CD4/CD8 ratio and the number of Sézary cells revealed that a reduction of several parameters significantly correlated with response to treatment. The parameters which correlated best with response were number of Sézary cells, CD4/CD8 ratio and WBC., Conclusions: The investigated combination therapy was effective and well-tolerated in a subgroup of SS patients but needs to be evaluated in a larger patient population.

Background: Treatment of choice for non-melanoma skin cancers is surgical excision. No study has analyzed the impact of the dermatologic surgeon's experience on the postoperative outcome., Patients and Methods: In a single center, retrospective study, 196 cases of non-melanoma skin cancer of the head and neck treated with micrographically-controlled surgery were categorized with regard to type of tumor, location, size of defect, number of stages, complications, recurrence rate and cosmetic result. These data were analyzed in respect of the surgeon's experience (dermatology attendings [AT], senior residents with experience in dermatosurgery [SR], junior residents with less experience in dermatosurgery [JR])., Results: AT and SR excised tumors in toto at roughly the same rate (AT: 42/75; SR: 59/104), JR less frequently (3/6). The patients graded 97% of the scars as very good to satisfactory. The grading of smaller defects (< 4 cm(2)) was not influenced by the surgeon's experience. Larger defects were graded equally in the two groups AT and SR. The complication rate was similar in all three groups, even though larger defects were treated by the attendings (AT)., Conclusions: Micrographically-controlled surgery followed by plastic reconstruction is the treatment of choice for non-melanoma skin tumors of the head and neck area. Cosmetic results are excellent. Minor procedures can be performed by residents during their training; larger defects require more experience in dermatosurgery.

Summary: Systemic lupus erythematosus and subacute cutaneous lupus erythematosus (SCLE) occasionally evolve as adverse reactions to a large variety of chemically different drugs. We here report on a 76-year-old woman who developed SCLE within 10 days after initiation of oral terbinafine. Analysis of the 27 cases of terbinafine-induced SCLE in the literature revealed that this disorder has been reported 6 times more often in females than in males. Skin lesions evolved on average around 7 weeks after starting the drug. In 79% of the cases ANA could be detected while antibodies against Ro/SS-A and La/SS-B were found in 86% and 39%, respectively. Remarkably, anti-histone antibodies were present in only 29%. In all cases terbinafine-induced SCLE resolved after discontinuation of the triggering agent. Systemic treatment with anti-malarials and/or corticosteroids does not appear to be mandatory.

A 58-year-old patient presented with both annular and polycyclic as well as vesicular lesions. Histology revealed an interface dermatitis with focal hyperkeratosis and subepidermal blistering. Antinuclear antibodies were elevated (1 : 1280) and autoantibodies against Ro-SS-A were found. Based on these findings we made a diagnosis of subacute cutaneous lupus erythematosus (SCLE) with blister formation. Additionally, we diagnosed porphyria cutanea tarda (PCT) triggered by alcohol abuse. Treatment with systemic corticosteroids and low-dose hydroxy-chloroquine led to rapid resolution of the skin changes. SCLE with blister formation is a rare cause of bullous skin eruptions and has to be distinguished from bullous autoimmune diseases as well as from bullous SLE. Recognition of concomitant PCT, which may be associated with all forms of LE, is especially important because of the therapeutic implications, since a reduced dosage of antimalarials is required.

Juvenile xanthogranulomas are a rare disease entity within the spectrum of cutaneous non-Langerhans cell histiocytoses characterized by single or multiple cutaneous xanthogranulomas without further organ involvement. A 16-year-old girl developed multiple xanthogranulomas in various skin regions, especially the trunk and the flexural areas, over a period of 6 months. The clinical diagnosis was confirmed by H&E histology, showing a histiocytic infiltrate admixed with foam cells and Touton giant cells, and by immunohistochemistry using anti-bodies to stabilin-1 whose expression is highly specific for cutaneous non-Langerhans cell histiocytoses. No diabetes insipidus, pituitary hyperplasia or paraproteinemia were observed. Skin lesions were treated with a CO(2) laser and did not reappear during a 5 years follow-up period.

Angioma serpiginosum, first described by Hutchinson in 1889, is a rare benign vascular nevus with dilatation and proliferation of the capillaries in the upper dermis. A 15-year-old boy presented with an angioma serpiginosum on the right side of the body following the lines of Blaschko. Both the clinical pattern and the appearance in a male are unusual. Treatment with IPL technology (intense pulsed light), which emits polychromatic light from a high-intensity flashlamp, proved to be an effective approach.

Cutaneous T-cell lymphoma is an extra-nodal non-Hodgkin lymphoma of mature T cells. These tumor cells home to and persist in the skin,producing a broad spectrum of clinical entities. Recent results of basic research on tumor biology and tumor immunology as well as molecular genetics of cutaneous T-cell lymphoma have fostered the development of new therapeutic approaches. Several clinical trials testing these targeted therapies have shown encouraging results. This article provides an overview of recent research developments and therapeutic strategies for cutaneous T-cell lymphoma.

Pyoderma gangrenosum is a chronic, noninfectious, ulcerating cutaneous disease of unknown etiology usually presenting with multiple lesions on the legs and trunk. Solitary lesions in other locations are rare and therefore hard to diagnose. A 78-year-old and a 81-year-old woman with extensive scalp necrosis were both diagnosed as pyoderma gangrenosum after exclusion of other differential diagnostic possibilities. The separate diagnosis of malignant pyoderma for this disease state no longer seems justified. Scalp necrosis is infrequently seen in dermatological patients; most previous reports describe it in giant cell arteritis. Other differential diagnoses include viral, bacterial and mycotic infections as well as erosive pustular dermatosis of the scalp. In conclusion, we again draw attention to unilesional pyoderma gangrenosum of the scalp as a rare disease entity. Immunosuppressive drugs are an effective treatment modality.

Pityriasis rubra pilaris (PRP) is a rare idiopathic erythematosquamous disorder. Griffiths proposed five clinical and prognostic forms: (1) classic adult, (2) atypical adult, (3) classic juvenile, (4) circumscribed juvenile and (5) atypical juvenile. A 2 1/2 year old boy presented with type 3 PRP; as is typical, the skin eruption was preceded by an infectious disorder. Although type 3 PRP normally shows spontaneous resolution after several months to years, our young patient had a severe and protracted course, only responding to systemic retinoids.

Background: Mugwort (Artemisia vulgaris) has traditionally been used as a spice, vegetable and as a herbal medicine. The main representatives of the Artemisia family besides Artemisia vulgaris include Artemisia absinthum and Artemisia dracunculus (estragon). Mugwort pollen allergens are important in triggering late summer and fall pollinosis; in addition cross reactivity occurs between Artemisia vulgaris pollen allergens and celery, carrottes and certain spices belonging to the family of Umbelliferae., Patients: A florist with a pre-existing sunflower allergy developed a life-threatening glottal edema after occupational contact with mugwort. She did not suffer from an oral allergy syndrome towards mugwort pollen cross allergens., Results: Skin testing (prick and scratch testing) revealed a strong sensitisation against mugwort and estragon. Specific IgE antibodies against mugwort, sunflower, carrots, celery, fennel and anis were elevated in the peripheral blood., Conclusions: The observation of a severe mugwort allergy with life-threatening complications in a florist underscores the high allergenic potential of Artemisia vulgaris and documents for the first time the occupational significance of this allergy.