BACKGROUND:Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood.OBJECTIVES:To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma.METHODS:Single-cell RNA sequencing (scRNA-seq) was performed and combined with T-cell and B-cell receptor sequencing.RESULTS:We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behaviour.CONCLUSIONS:These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.

Background Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. Objectives To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. Methods This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. Results A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naivety, its superiority vanished and drug survival rates were similar for ixekizumab (91.6%), secukinumab (90.2%) and ustekinumab (92.8%), all of them superior to adalimumab (76.5%) and etanercept (71 .9%) at 12 months and beyond. Besides biologic non-naivety (2 .10, P < 0.001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1.6, P = 0.001) and female gender (1.50, P = 0 .019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1.12, P = 0.21). Conclusions The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

BACKGROUND:Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging. OBJECTIVES:To develop a prognostic index for MF. METHODS:Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. RESULTS:In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. CONCLUSIONS:This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

BackgroundPrimary cutaneous lymphomas (PCL) are a heterogenous group of rare lymphoid neoplasms with incomplete information on global and regional prevalence. The recently introduced lymphoma classifications define distinctive clinicopathological disease entities that should allow for more accurate epidemiological assessment.ObjectiveThe aim of this study was to evaluate the prevalence and clinical spectrum of PCL diagnosed and treated at the Department of Dermatology and Venereology in St. Polten, Lower Austria, a dermatology referral centre providing secondary and tertiary care for a population of about 600000.MethodsIn this retrospective study pathology reports, electronically archived between 2006 and 2013, were screened for the terms lymphoma, mycosis fungoides (MF) and lymphomatoid papulosis (LyP). Patients were diagnosed according to the current WHO-EORTC classification for cutaneous lymphomas and results were compared with data from European, US and Asian centres.ResultsAmong 86 patients with PCL (age 58.317.35years, mean +/- SD; women 38%, n=33; men 62%, n=53) 83% (n=71) were classified as cutaneous T-cell lymphomas (CTCL) and 17% (n=15) as cutaneous B-cell lymphomas (CBCL). Nine patients with CTCL showed associated haematological disorders and malignomas. Among 47 MF patients following variants were observed: pilotropic MF (n=2), follicular mucinosis (n=1), unilesional MF (n=1), large-cell transformation (n=3), erythrodermic MF (n=1), poikilodermatous MF (n=2) and posttransplant lymphoproliferative disorder (CD8(+) MF with gamma/delta phenotype after renal transplantation) (n=1). One patient had MF concurrent with lymphomatoid papulosis. The group of CBCL comprised six cases (40%) of PCMZL and PCFCL each, 20% (n=3) were classified as PCLBCL, LT.ConclusionThis study for the first time provides data on the distribution of PCL clinicopathologic variants and stages according to the latest classification and staging systems in an Austrian referral centre.

BACKGROUND:Actinic keratoses (AKs) are common precursors of squamous cell carcinomas (SCCs) of the skin making them an important public health issue with information on their prevalence widely lacking.OBJECTIVES:To define the prevalence of AK in dermatology outpatients in Austria and to identify more accurately the target population for AK screening, treatment and prevention.METHODS:Each of the 48 randomly selected Austrian office-based dermatologists simultaneously screened 100 consecutive patients (aged ≥ 30 years) for the presence of AK.RESULTS:In total, 4449 evaluable patients showed an overall AK prevalence of 31·0%, which was higher in men (39·2%) than in women (24·3%) and increased with age in both sexes. AK distribution among sun-exposed body sites and extent of disease varied with sex and region.CONCLUSIONS:In Austria, AKs are common among dermatology outpatients, who have access to professional education and treatment. Investigations regarding the efficacy of routine AK screening in dermatology outpatients for the prevention of invasive SCC is warranted.

INTRODUCTION: Primary melanocytic tumours of the leptomeninges are rare diseases. The WHO classification of 2007 described four entities: diffuse melanocytosis, melanocytoma, malignant melanoma and meningeal melanomatosis. Meningeal melanocytosis is a benign proliferation of melanocytes with a risk of malignant transformation and is often associated with neurocutaneos melanosis. CASE REPORT: A 65-year-old male patient presented with low back pain and disturbed micturition. Neurological examination revealed left sided S1- sensory radiculopathy. His medical history was unremarkable. MRI of the lumbar spine showed a contrast-enhancing intrathecal tumour of the conus medullaris and MRI of the brain was suspicious of neoplastic meningitis. Spinal surgery exhibited a brown tumour mass with diffuse spreading of pigmented lesions along the arachnoidea. Histological, immunohistochemical, and molecular analyses showed an intrathecal melanoma with a wild-type BRAF genotype. Dermatological examination was unremarkable. Lumbar stereotactic radiotherapy was applied. Subsequently, 3 cycles of temozolomide (150mg/m2 on 5 days out of 28) and bi-weekly intrathecal liposomal cytarabine were administered. Despite the poor prognosis of neoplastic meningitis in melanoma, the patient survived without clinical for more than one year. 15 months after the initial diagnosis spinal MRI showed a local relapse and a second surgery was performed. This time molecular analysis of the tumor revealed the presence of the BRAF V600E mutation. Due to the initially slow tumor progression treatment with B-Raf inhibitors was withheld and immunotherapy with the anti-CTLA-4 antibody ipilimumab was initiated together with stereotactic radiotherapy of the conus medullaris. Three months later, the patient complained about diplopia and dizziness. Neurological examination revealed oculomotor nerve palsy. MRI of the brain showed a meningeal contrast-enhancement in the brainstem area. The B-Raf inhibitor vemurafenib was initiated in combination with intrathecally administered liposomal cytarabine and whole brain radiotherapy. Despite this the patient's condition deteriorated and he died two weeks later. Considering the long progression-free interval and the diffuse intrathecal melanocytic spread, the initial diagnosis of neoplastic meningitis was re-evaluated. Differential diagnoses include neoplastic meningitis from an unknown primary melanoma and malignant transformation of leptomeningeal melanocytosis. Retrospectively, we speculate that the patient had a leptomeningeal melanocytosis and consecutive malignant transformation. Treatment options are palliative and include intrathecal and systemic chemotherapy, radiotherapy, immunotherapy, as well as kinase inhibitors. Since evidence based guidelines are lacking therapy has to be selected on an individual basis.

Background: Existing sweat tests are either cumbersome, require dedicated technical equipment and/or do not give reliable quantitative results. The present study was performed to develop and describe a rapid and simple test for a practical and quantitative evaluation of sweating. Methods: Cobalt chloride patches were used to collect sweat during exercise and after application of aluminum hydrochloride. Color change from blue to red was recorded and quantified, and the amount of sweat was calculated from a standard curve. Results: Cobalt-chloride-containing patches evaluated with standard office equipment provide a rapid, simple and highly sensitive method for the quantitative measurement of sweating. Conclusions: Possible applications that need to be evaluated in further studies are the diagnosis and monitoring of diseases associated with disordered sweat production and the evaluation of antiperspirants.

BackgroundMonitoring and repeated staging is of substantial importance in many patients with primary cutaneous T-cell lymphomas (CTCL). For primary cutaneous B-cell lymphomas (CBCL), extensive initial staging is the mainstay for correct diagnosis.AimTo evaluate the value of somatostatin receptor scintigraphy using the radiolabeled somatostatin analog 111In-pentetreotide in comparison to conventional imaging methods for the staging of patients with primary CTCL and primary CBCL.MethodsTwenty-two patients (15 patients with histologically verified CTCL and 7 patients with histologically verified CBCL) were included. Stage of disease was established by physical examination, laboratory screening, skin inspection, palpation of superficial lymph nodes, sonography and computed tomography (CT) in patients with advanced clinical stage. Focally elevated tracer uptake of 111In-pentetreotide was compared to common imaging modalities, physical aspect and digital photographs of the respective skin lesions.ResultsOf the 15 patients with CTCL, only 4 (27%) showed positive scintigraphic results, but not in all sites of lymphomatous involvement. None of the five patients with mycosis fungoides in stage I, nor any of the four patients with Sezary syndrome, had a positive 111In- pentetreotide scan. Of the seven patients with CBCL three positive scintigraphic results (43%) could be obtained: in two patients with a follicular center lymphoma and one patient with a diffuse large B-cell lymphoma - leg type, but again not in all apparent sites of lymphoma.ConclusionsBased on our results, we do not recommend the use of somatostatin receptor scintigraphy for routine staging of patients with CTCL and CBCL. As our series includes only 22 patients, and the number of patients with rarer variants of CTCL was rather small, it might be too premature to abandon SST-R in the staging of patients with cutaneous lymphomas.

Background The Langerhans cell (LC) hypothesis suggests that cutaneous T-cell lymphomas (CTCL) are diseases of chronic T-cell stimulation by LC-mediated antigen presentation.Objective To investigate a broad panel of CTCL and cutaneous B-cell lymphomas (CBCL) for the spatial association of langerin(+) dendritic cells (DC) with T and B cells in the skin, respectively.Methods Fifty-five specimens of CTCL and 10 of CBCL were double-stained with monoclonal antibodies against langerin and CD3 or CD20, respectively, and evaluated by confocal laser scan microscopy.Results Dermal infiltrates in mycosis fungoides (n = 38), primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (n = 3) and primary cutaneous peripheral T-cell lymphoma, unspecified (n = 3) were characterized by a high frequency of dermal langerin(+) DCs. These cells were exclusively present in the malignant infiltrates. No direct co-localization of CD3 and langerin could be resolved. Dermal langerin(+) cells were detected only in one of six primary cutaneous anaplastic large cell lymphomas (C-ALCL), characterized by epidermotropism. In other C-ALCL cases (five of six), in lymphomatoid papulosis (n = 3), subcutaneous panniculitis-like T-cell lymphoma (n = 2), and all variants of CBCL no dermal langerin(+) DCs could be found.Conclusions Langerin(+) DCs are abundant in the dermal infiltrates of T-cell lymphomas with specific involvement of the epidermis. This might indicate that immature LC and neoplastic T cells interact and gives rise to further studies to characterize the phenotype of the langerin(+) cell population described here and its role in the pathology of CTCL. Received: 4 July 2010; Accepted: 22 September 2010

BACKGROUND We have carried out a retrospective analysis to evaluate the therapeutic value of the anti-CD20 antibody rituximab in 16 consecutive patients with primary cutaneous CD20+ B-cell lymphomas. PATIENTS AND METHODS Sixteen patients (4 females, 12 males) with a median age of 54 years received systemic therapy with rituximab 375 mg/m(2) once weekly for four or six consecutive weeks. Eleven patients had primary cutaneous follicle center cell lymphoma and five patients had a primary cutaneous marginal zone B-cell lymphoma. RESULTS Of the 16 patients with PCBCL, 14 patients (87.5%) achieved complete remission (CR). In two patients, partial remission was obtained and additional focal radiotherapy was applied, which resulted in final CR. Five to 14 (35%) patients with CR relapsed, in an interval between 6 and 37 months. There were no severe side-effects. CONCLUSIONS On the basis of our results, single-agent treatment with i.v. rituximab appears to be feasible and safe and results in a high rate of durable remissions. Judging from our data, it appears to be an attractive treatment option and should be directly compared with local radiotherapy.

BACKGROUND:Photodegradation of folic acid (FA) by ultraviolet (UV) radiation is a well-documented photochemical reaction, and decreased serum levels of FA have been found in patients receiving photochemotherapy (psoralen plus UVA). During extracorporeal photopheresis (ECP) leucocytes and plasma are subjected to 8-methoxypsoralen (8-MOP) plus UVA.OBJECTIVES:To investigate whether ECP leads to the photodegradation of FA in the extracorporeal system.METHODS:In 30 patients undergoing ECP on two consecutive days the FA levels were measured in the extracorporeal collected plasma prior to and after UVA exposure. Healthy donor plasma was exposed to 8-MOP and increasing doses of UVA in vitro. In five patients serum folate levels were determined before and after ECP.RESULTS:We found a mean reduction of 44% and 46% on the first and second day of treatment, respectively. This effect could be reproduced in vitro: the irradiation of healthy donor plasma with UVA led to a dose-dependent reduction of FA of up to 54.75% at 16 J cm(-2). This was independent of the presence of 8-MOP and the base concentration of 5-methyltetrahydrofolate; minimal changes were observed for vitamin B(12) and homocysteine, not undergoing photodegradation. Serum folate levels did not change significantly before and after ECP.CONCLUSIONS:We conclude that extracorporeal exposure of plasma to UVA during ECP leads to photodegradation of FA. Further investigations are required to determine the biological effects of folate photoproducts and whether clinically relevant loss of FA might be a consequence of ECP.