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Aim To identify the most common therapeutic options for the treatment of early-stage mycosis fungoides in Spain, quantify their associated healthcare resource use and costs. Methods After reviewing the literature, a panel of 6 Spanish clinical dermatologists validated the treatments and healthcare resource use through a structured questionnaire. Individual responses were collected, analyzed and presented into a face-to-face meeting in order to reach a consensus. Cost categories considered were: drug acquisition and administration, photo/radiotherapy session and maintenance, clinical follow-up visits and laboratory tests. Costs were expressed in euros from 2018. The Spanish National Health System perspective was considered, taking into account direct health costs and time horizons of 1, 3 and 6 months. Results Costs for the skin-directed treatments (SDT) assessed at 1, 3 and 6 months, were: Topical carmustine [€6,593.36, €19,780.09 and €27,592.78]; Phototherapy with psoralens and ultraviolet A light (PUVA) [€1,098.68, €2,999.99 and €3,187.60]; Narrow-band ultraviolet B phototherapy [€1,657.47, €4,842.10 and €4,842.10]; Total skin electron beam therapy (TSEBT) [€6,796.45, €7,913.34 and €7,913.34]. Cost for topical corticosteroids, being considered an adjuvant option, were €17.16, €51.49 and €102.97. Costs for the assessed systemic treatments alone or in combination with SDT at 1, 3 and 6 months, were: Systemic retinoids [€2,026.03, €5,206.63 and €7,426.42]; Systemic retinoids + PUVA phototherapy [€3,066.50, €8,271.26 and €10,046.58]; Interferon alfa + PUVA phototherapy [€1,541.09, €5,167.57 and €6,404.55]. Conclusion According to the Spanish clinical practice, phototherapies in monotherapy were the treatments with the lowest associated costs regardless of the time horizon considered. TSEBT turned out as the treatment with the highest associated costs when considering 1 month. However, while considering 3 and 6 months the treatment with the highest associated costs was topical carmustine. The results of this analysis may provide critical information to measure the disease burden, to detect unmet medical needs and to advocate towards better treatments for this rare disease.

Background/Objectives Primary cutaneous lymphomas are rare in pediatric patients. The clinical and histopathological manifestations may differ from those in adults. Due to their low frequency and the insidious clinical picture, the diagnosis is usually delayed. The Spanish Primary Cutaneous Lymphoma Registry was initiated in 2016 as a multicenter registry that would allow better insight into the epidemiological, clinical, histopathological, and treatment response characteristics of patients with primary cutaneous lymphomas. Methods We conducted a prospective observational cohort study of primary cutaneous lymphomas in pediatric patients participating in the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry. Results At the time of the analysis, 10 patients under 18 years of age out of 799 all-age cases (1.25%) had been included in the registry (7 males, 3 females). The mean age at diagnosis was 9.7 years (SD: 4.8). Seven (70%) had mycosis fungoides, 2 of them had the folliculotropic variant; and 3 (30%) had primary cutaneous marginal zone B-cell lymphoma. Conclusions Primary cutaneous lymphomas are extremely rare in pediatric patients and usually have a good prognosis. Therefore, a high level of suspicion is necessary for the diagnosis. We suggest management by experienced physicians and follow-up into adulthood.

Background Primary cutaneous follicular center-cell lymphoma (PCFCL) is one of the most common types of cutaneous B-cell lymphoma. Differences in immunohistochemical expression of BCL2 and CD10 antigens along with the presence of t(14:18) translocation in neoplastic cells have been postulated as relevant clues in differentiating PCFCL from cutaneous lesions secondary to a systemic follicular lymphoma (SCFL). The aim of this study is to evaluate the significance and usefulness of these parameters in a large series of patients. Methods Patients with PCFCL and SCFL diagnosed at three university hospitals in Barcelona, from 2000 to 2015 were reviewed. Clinical, histopathological, immunophenotypical, genetic, and outcome parameters were analyzed. Results Eighty-one cases (59 PCFCL and 22 SCFL) were included. There were no significant differences between PCFCL and SCFL cases regarding clinical presentation, site of involvement, or predominant type of skin lesions. Most patients in both groups showed positivity for BCL2 and CD10, but strong expression of BCL2 and CD10 was associated with SCFL cases. Although more frequent in SCFL, a small proportion of PCFCL cases also showed the t(14:18) on FISH analysis. Conclusion The intensity of BCL2 expression was found to be the single most valuable clue in differentiating PCFCL from SCFL cases on histopathological grounds.

Background The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF).Objectives To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures.Methods In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review.Results The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81 center dot 5%), while a smaller percentage (44 cases, 11 center dot 1%) received systemic therapy. Expectant observation was used in 7 center dot 3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0 center dot 001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0 center dot 001), higher modified Severity Weighted Assessment Tool (> 10, 15%

While some papers report an increased risk of COVID-19 and worse outcomes1 in oncological patients, others have found no differences2 . We are not aware of studies assessing risk for COVID-19 and clinical outcomes of patients with Primary Cutaneous Lymphomas (PCL).

Background Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis (CT) serovars L1, L2, and L3 and is endemic among men who have sex with men (MSM) in Europe. We evaluated weekly oral azithromycin 1 g for 3 weeks as a treatment for LGV proctitis. Methods This is an open clinical trial with convenience allocation according to treating physician preferences. Adults with clinical proctitis received a single dose of 1 g of intramuscular ceftriaxone and were subsequently allocated to receive (i) doxycycline 100 mg twice daily for 21 days (Doxycycline group) or (ii) azithromycin 1 g orally once weekly for 3 weeks (Azithromycin group). LGV cure (primary endpoint) was defined as resolution of symptoms at week 6 (clinical cure, LGV-CC), with an additional supporting negative rectal polymerase chain reaction (PCR) at week 4 (microbiological cure, LGV-MC), if available. Results One hundred and twenty-five individuals with LGV clinical proctitis were included. All were MSM, and 96% were living with human immunodeficiency virus (HIV). Eighty-two were in the Azithromycin group, and 43 were in the Doxycycline group. LGV cure on a modified intention-to-treat analysis (primary endpoint), occurred in 80 of 82 (98%) in the Azithromycin group versus 41 of 43 (95%) in the Doxycycline group (treatment difference [95% confidence interval {CI}] 2.2% [−3.2, 13.2]). LGV-MC occurred in 70 of 72 (97%) vs 15 of 15 (100%) in the Azithromycin group and Doxycycline group, respectively (treatment difference [95% CI] −2.8% [−9.6; 17.7]). Adverse events were similar in both treatment groups. Conclusions Our findings support extended azithromycin dosing as an alternative treatment option for symptomatic LGV proctitis and provides the rationale for future randomized trials.

BACKGROUND Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE To identify prognostic factors for specific survival in patients with PCALCL. METHODS Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P

Mogamulizumab is an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody that has been approved for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sezary syndrome (SS) who have been treated with at least 1 prior line of therapy. We present the case of a 76-year-old woman diagnosed with SS refractory to all prior lines of therapies, who presented a prolonged response to Mogamulizumab in the peripheral blood, skin, and lymph nodes. However, after almost 1 year of treatment, the patient developed psoriasis-like patches (confirmed by histology), and arthritis mainly in the shoulder girdle, hip and cervical region diagnosed by MRI and ultrasonography as a polymyalgia rheumatica-like. After consensus between hematologists, dermatologists and rheumatologists, the patient was treated with low-dose prednisone (5–10 mg) daily and mogamulizumab was tapered (dose widening to every two months), with great control of side effects and maintenance of complete response of her SS (skin, peripheral blood, and lymph nodes) until now. Mogamulizumab has been shown to be an effective and well tolerated therapy for patients with relapsed and refractory MF/SS with excellent activity in the circulating component of the disease. Common adverse events include infusion reactions and drug eruptions and increase of the risk of immune-mediated complications such as autoimmune disease and acute graft-versus-host disease following transplantation. However, we still must be aware of new drug eruptions and side effects that require prompt diagnosis and treatment.

Background Skin problems are among the most frequent reasons for seeking medical attention in primary care. In recent years, as a result of the process of adapting medical curricula to the requirements of the European Higher Education Area, the amount of time students spend learning the concepts of dermatology has been reduced in many universities. Material and methods In order to reach a consensus on core content for undergraduate education in dermatology, we sent a survey to the 57 members of the instructors’ group of the Spanish Academy of Dermatology and Venereology (AEDV), asking their opinions on what objectives should be set for a dermatology course in Spain. A total of 131 previously selected objectives were listed. We then applied the Delphi method to achieve consensus on which ones the respondents considered important or very important (score ≥ 4 on a Likert scale). Results Nineteen responses (33%) were received. On the second round of the Delphi process, 68 objectives achieved average scores of at least 4. The respondents emphasized that graduates should understand the structure and functions of the skin and know about bacterial, viral, and fungal skin infections, the most common sexually transmitted diseases (STDs), and the 4 main inflammatory dermatoses. Students should also learn about common complaints, such as itching and bald patches; the management of dermatologic emergencies; purpura and erythema nodosum as signs of internal disease; and the prevention of STDs and skin cancer. During clinical clerkships students should acquire the communication skills they will need to interview patients, write up a patient's medical history, and refer the patient to a specialist. Conclusions The AEDV's group of instructors have defined their recommendations on the core content that medical faculties should adopt for the undergraduate subject of dermatology in Spain.

Pancreatic panniculitis is a rare type that only occurs in 2-3% of all patients with pancreatic diseases. It is usually described in association with benign pancreatic disease and less commonly in association with pancreatic carcinoma. We describe a case of pancreatic panniculitis as the first manifestation of underlying ampullary adenocarcinoma and a new case of pancreatitis, panniculitis and polyarthritis (PPP-Syndrome). Pancreatic panniculitis may be the cutaneous manifestation of pancreatic allograft rejection after simultaneous pancreas-kidney transplantation.

Background and objective: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. Patients and methods: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. Results: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sezary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous [D30' T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid paputosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). Conclusion: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group. (C) 2018 AEDV. Published by Elsevier Espana, S.L.U. All rights reserved.

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma of mature cytotoxic T cells. Initially, patients with SPTCL were treated with doxorubicin-based polychemotherapy. Objective: To analyze clinical, biologic, immunophenotypical, molecular, imaging, treatment, and outcome data reflecting the current state of knowledge. Methods: A retrospective multicenter study of 16 patients with SPTCL that was diagnosed between 1996 and 2016. Results: The female-to-male ratio was 1.7. The median age at diagnosis was 46.5 years. Patients presented with multiple nodular or plaque-like lesions preferentially affecting the legs and/or trunk. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3(+), CD4(-), CD8(+), CD56(-), TIA1 cytotoxic granule associated RNA binding protein 1-positive phenotype and high proliferation rate. SPTCL was associated with autoimmune diseases in 25% of patients, and with the development of hemophagocytic syndrome in 18% of patients. Oral steroids alone or in combination with low-dose methotrexate or cyclosporine A were the most common initial treatment, achieving a complete response in 85% of the treated patients. The median follow-up time was 14 months. The 5-year disease-specific survival rate was 85.7%. Limitations: This was a retrospective study. Conclusions: SPTCL has an excellent prognosis. Immunosuppressive agents can be considered for first-line treatment.

Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients.

Background and objectives Cutaneous leishmaniasis is the most common form of leishmaniasis, which is endemic in Spain. The aim of this study was to evaluate the epidemiological and clinical characteristics of cutaneous leishmaniasis seen in our hospital over a period of 20 years, with a particular focus on clinical differences according to immune status and origin of infection Materials and methods We performed a chart review of 67 cases of cutaneous leishmaniasis diagnosed between 1992 and 2012. Follow-up data were available for 54 patients. Results Fifty-four patients with cutaneous leishmaniasis were included in the study. Of these, 26 had been diagnosed between 1992 and 2002 and 28 between 2003 and 2012. The mean age at diagnosis was 49 years, there was a predominance of male patients, and the mean time from onset of symptoms to consultation was 3 months. The most common clinical manifestations were plaques and ulcers. Most of the immunodepressed patients and patients with imported leishmaniasis had skin ulcers and/or multiple lesions. During the first decade of the study, diagnosis was based on clinical and histologic findings. These were supported by molecular techniques in the second decade. Pentavalent antimonials were the treatment of choice, producing good results and very few adverse effects Conclusion The number of patients with cutaneous leishmaniasis and with compromised immune status was similar in the periods 1992-2002 and 2003-2013, but more cases of imported leishmaniasis were diagnosed in the second period. Patients with ulcers and/or multiple lesions should be evaluated to rule out immunosuppression or infection by Leishmania species from other parts of the world. Both systemic and intralesional meglumine antimonate was effective and safe

A case of a 78-year-old woman with a CD8-positive peripheral T-cell lymphoma with aberrant expression of CD20 associated with follicular lymphoma in situ (FLIS) is reported. The neoplasm presented initially as cutaneous macules, papules, plaques and nodules. A skin biopsy was performed and the diagnosis of peripheral T-cell lymphoma (PTCl) with aberrant expression of CD20 was made. The staging procedures included an excisional inguinal lymph node biopsy that showed findings similar to those of the previous diagnosis. In addition, FLIS was identified. The clinicopathologic features of PTCLs with aberrant CD20 expression involving the skin as well as this uncommon association are reviewed.

Urticaria is a common skin disease characterized by transient appearance of itchy smooth and slightly elevated erythematous papules or plaques (wheals). It results from transient extravasation of plasma into the dermis that leads to dermal edema. By definition, individual lesions resolve without scarring in less than 24 hours. The diagnosis is based on detailed patient history and physical examination and skin biopsy is rarely required to confirm the diagnosis. This article is protected by copyright. All rights reserved.

Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P

Aprepitant has shown a promising anti-itch activity in several cases of cutaneous T-cell lymphomas (CTCLs)1-8. We sought to determine its antipruritic efficacy in a large multicenter series of CTCLs patients with refractory pruritus and, secondarily, to define possible clinical predictors of response.A retrospective, analytical review of the Spanish Working Group on Cutaneous Lymphoma database was designed to collect patients with CTCLs and refractory pruritus, treated with aprepitant from 2009 to 2013. This article is protected by copyright. All rights reserved.

Importance Hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives To analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants This case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures Primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results Among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.

Background: Intravenous rituximab is a safe and effective option for the treatment of systemic non-Hodgkin B-cell lymphoma. The effectiveness of intralesional rituximab (ILR) in primary cutaneous B-cell lymphomas (PCBL) has been described in a small number of patients. Objectives: To evaluate the effectiveness, tolerance and adverse effects of ILR in patients with follicle centre (FCL) and marginal zone (MZL) PCBL. Methods: This was an epidemiological observational multicentre study of patients with PCBL treated with ILR. Results: Seventeen patients with MZL and 18 with FCL PCBL were included. The median number of lesions treated was two per patient. The treatment regimen used in 74% of the patients was a course of three injections in a single week at 1-month intervals. The dose per lesion and day of treatment was 10 mg in 71% of the patients. The median cumulative dose of rituximab per lesion was 60 mg (range 13-270) and per patient was 150 mg (range 20-360 mg). Complete response (CR) and partial response were achieved in 71% and 23% of patients, respectively. The median time to CR in patients who received 10 mg of ILR per lesion was 8 weeks. Similar response rates were observed in MZL and FCL. Median disease-free survival was 114.1 weeks. No parameters that significantly predicted CR were identified. Adverse reactions were recorded in 19 patients; the most frequent was localized pain at the injection site. Median follow-up was 21 months. Conclusions: Intralesional rituximab is a well-tolerated and effective treatment for FCL and MZL PCBL. It should be considered a useful alternative in patients with recurrent lesions and in which the sequelae of radiotherapy or surgery would be significant. © 2012 The Authors BJD © 2012 British Association of Dermatologists 2012.

Follicular lymphoma (FL), a typically nodal disease, can arise in extranodal sites in about 10% of cases. The present study aimed to analyse the main differential features of patients with primary extranodal FL. Thirty-nine patients with primary extranodal FL were identified from a series of 354 patients with FL diagnosed at a single institution and their main clinicobiological features were analysed. Twenty patients (5·6%) had a primary extranodal non-cutaneous FL, and 19 (5·4%) a cutaneous FL. BCL2(+) and CD10(+) expression and BCL2/IGHJ@ rearrangement were less frequently observed in cutaneous FL. Absence of 'B'-symptoms, early stage, absence of bone marrow involvement and low-risk Follicular Lymphoma International Prognostic Index (FLIPI) were more frequent in extranodal FL. Five-year overall survival (OS) was 100%, 83% and 78% for cutaneous, non-cutaneous and nodal FL, respectively. When stage I patients were analysed separately, no differences were seen in terms of OS. In multivariate analysis, FLIPI was the most important variable to predict outcome. In conclusion, extranodal FLs, particularly cutaneous, have particular clinico-biological features, which differentiate them from nodal cases. Nevertheless, primary site of the disease is not the main issue to predict outcome.

Background Cell adhesion molecules (CAMs) play a pivotal role in cutaneous localization of T cells. Tissue-selective localization of T lymphocytes to the skin is crucial for immune surveillance and in the pathogenesis of skin disorders. Objective To detect the profile of soluble CAMs in patients with cutaneous T-cell lymphoma (CTCL), we investigated the levels of intercellular adhesion molecule-1 (ICAM-1, soluble ICAM-1 [sICAM-1]); intercellular adhesion molecule-3 (sICAM-3); vascular cell adhesion molecule-1 (sVCAM-1); and E-selectin (sE-selectin) in sera from patients with T-cell–mediated skin diseases. Methods Serum levels of the 4 CAMs were measured by enzyme-linked immunosorbent assay in 42 participants including 11 patients with early stages of CTCL; 7 with advanced stages of CTCL including Sezary syndrome; 12 with inflammatory skin diseases (psoriasis and atopic dermatitis); 8 with skin diseases that may evolve into CTCL; and healthy individuals. Levels were correlated with biological parameters known as prognostic factors in non-Hodgkin lymphomas. Results In patients with CTCL, significantly increased levels of sICAM-1 and sICAM-3 were found when compared with healthy individuals and patients with inflammatory dermatosis. Soluble E-selectin and sVCAM-1 levels were not increased. There were significant positive correlations between sICAM-1 and sICAM-3 levels and each of them with β2-microglobulin levels. Limitations Limited number of patients was a limitation. Conclusion There is a distinct profile of soluble CAMs in patients with CTCL. However, future studies with a larger group of patients are needed to confirm these findings. We propose that high sICAM-1 and sICAM-3 levels have important implications in the context of immune response and immune surveillance in these patients.

The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions.

Resumen Introduccion La dermatomiositis (DM) es una enfermedad de origen autoinmune, incluida en el grupo de las miopatias inflamatorias idiopaticas. En el control clinico de este proceso se precisan marcadores que permitan determinar el grado de actividad de la enfermedad, facilitando asi el ajuste a la terapia inmunomoduladora. Se analiza la relacion entre los productos de activacion del complemento (PAC) y la actividad de la DM y su utilidad en el seguimiento de la enfermedad y en la prediccion de las reagudizaciones en relacion a los parametros bioquimicos habituales. Material y metodos Se estudiaron 16 pacientes con DM, que fueron seguidos periodicamente. En cada revision se establecio el grado de actividad cutanea y muscular del proceso, y se correlaciono dicha actividad con los niveles plasmaticos de C3a y C5b-9, determinados mediante tecnica de ELISA. Resultados Si bien se obtuvo cierta correlacion entre la actividad del proceso y los niveles plasmaticos de C3a y C5b-9, la intensidad de dicha correlacion no supero la obtenida por los marcadores bioquimicos tradicionales. En la capacidad de prediccion de reagudizaciones, C3a se mostro como el marcador mas sensible (100 %), con una especificidad suficiente (83,3 %). Conclusiones C3a y en menor medida C5b-9 serian de utilidad en la identificacion de pacientes con DM especialmente activas, asi como en la prediccion de reagudizaciones del proceso. Sin embargo, no tienen una utilidad superior al resto de marcadores bioquimicos como marcadores de actividad actual.

In the newly revised World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) consensus classification for cutaneous lymphomas, cutaneous gamma/delta T-cell lymphoma (CGD-TCL) has been included as a provisional entity. This type of lymphomas, when involving the subcutaneous fat, can mimic both clinically and histologically other more indolent conditions, such as subcutaneous panniculitic T-cell lymphomas (SPTCL) and lupus erythematosus profundus (LEP), and multiple biopsies may be needed to obtain a correct diagnosis. A good correlation of the clinical data with the histopathology and immunohistochemistry are required for diagnosis. Herein, we describe a patient whose initial histopathologic findings ressembled LEP but presented an aggressive clinical course. A new biopsy was performed during the follow-up, and a final diagnosis of CGD-TCL was made.

Eosinophilic ulcer of the oral mucosa (EUOM), also known as traumatic ulcerative granuloma with stromal eosinophilia or Riga-Fede disease, is an uncommon benign self-limited lesion poorly described in the dermatological literature. It probably includes a spectrum of related disorders presenting as an ulcer with elevated indurated borders affecting the tongue, oral mucosa or lip. Histopathological findings are characteristic and consist of eosinophil-rich mixed infiltrates accompanied by a population of large mononuclear cells whose origins have been a matter of debate. Immunohistochemical studies of these cells have suggested a myofibroblastic or histiocytic origin. We present a 93-year-old woman with two episodes of self-healing ulcers on the upper lip and on the lingual mucosa, respectively. Histopathological findings on both biopsies were consistent with EUOM and showed the presence of large atypical CD30+ lymphocytes. Some recent reports have also shown positivity for the CD30 antigen, raising the possibility that a subset of EUOM could be included within the spectrum of CD30+ lymphoproliferative disorders. This finding most likely suggests that EUOM can represent another histological simulator of CD30+ lymphoproliferative disorders.

Several reviews and guidelines on the management of mycosis fungoides and Sézary syndrome (MF/SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and no European consensus has yet been established. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. In order to summarise the available evidence and review 'best practices' from each national group, the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European guidelines for the treatment of MF/SS. This article reviews the treatment regimens selected for inclusion in the guidelines and summarises the clinical data for treatments appropriate for each stage of MF/SS. Guideline recommendations are presented according to the quality of supporting data, as defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies are the most appropriate option for early-stage MF/SS and most patients can look forward to a normal life expectancy. Patients with advanced disease should be encouraged to participate in clinical trials and maintenance of quality of life should be paramount.

Large series of patients with Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), have been reported infrequently because of its low incidence. Here we recorded several clinical, histopathological and immunophenotypical features of 29 cases of leukemic CTCL patients from four Dermatology Departments of Catalonia, Spain, and analyzed their prognostic value. Clinical data included sex, age, delay of SS diagnosis, previous diagnosis of lymphoma, B-symptoms, type of skin lesions, peripheral adenopathy, histologic evaluation of lymph node biopsy, visceral involvement, percentage of circulating Sézary cells, serum LDH and beta-2-microglobulin levels, first treatment and response, disease-free interval, further therapies and survival. Histopathological data examined were epidermotropism, depth and thickness of the infiltrate, cell size, adnexal involvement, presence of granuloma, eosinophils and plasma cells, mitotic rate. The percentage of CD45Ro, CD43, CD20, CD30 and CD8 positive dermal cells were also recorded. Survival showed a mean actuarial risk of 57% at 3 years and 38% at 5 years, with a median survival of 48 months. Analysis of actuarial survival demonstrated as following as features linked with a bad prognosis: fast evolution of the disease (from symptoms onset up to diagnosis) (p = 0.0274) raised levels of serum lactate dehydrogenase (p = 0.0379) and beta-2-microglobulin (p = 0.0151), the latter being the most important prognostic factor. In conclusion although SS had been traditionally considered as a low-grade lymphoma, the present study agrees with the recent classification rating SS as an aggressive type of CTCL with a poor prognosis. Our results show that some simple clinical and blood test data can be useful as prognostic indicators in this disease.

Summary Background Primary cutaneous marginal zone B-cell lymphoma (MZCL) has recently been described. Differentiation from follicular centre cell lymphomas and lymphocytomas is often difficult due to insufficient experience and a lack of large series of patients. Objectives To characterize primary cutaneous MZCL better, we report clinical, histopathological, immunophenotypic and molecular genetics features in a series of 22 patients. Methods All patients were treated and followed up at the same institution. Diagnosis of MZCL was based on the World Health Organization classification criteria. All samples were routinely tested with a wide panel of monoclonal antibodies. DNA was extracted from every sample following standard methods. IgH rearrangement and t(14;18)(q32;q21) studies were performed in all samples. Results Twenty-two patients (20 men, two women; mean age 50 years, range 24–77) were included. The mean follow-up was 43 months. Seventy per cent of patients presented with characteristic skin lesions on the trunk or extremities, consisting of deep red to violaceous infiltrated plaques, nodules or tumours frequently surrounded by diffuse or annular erythema. Four patients presented with lesions on the head and neck area. Two patients had disseminated skin lesions. The main histopathological features were non-epidermotropic, dense lymphocytic infiltrates mainly distributed in a nodular pattern. Adnexal involvement was usually present, with eventual formation of lymphoepithelial complexes. Cytologically, the infiltrate was polymorphous with marginal zone B cells and B-monocytoid cells. Blastoid CD30+ cells were often observed. Colonized reactive germinal centres and lymphoplasmocytoid differentiation were frequently present. Neoplastic cells were CD20+, CD79a+, CD5– and CD10–. Monotypic expression of light chains was observed in 18 cases (13 κ; five λ) . Clonal IgH rearrangements were detected in 14 cases. The bcl-2 mutation t(14;18)(q32;q21) was demonstrated in two cases. Most patients were treated with local radiotherapy. Complete response rate with this approach was 100%. Six patients (27%) had skin recurrences from 6 months to 8 years after first treatment. Five patients (23%) had extracutaneous involvement. Two of them had a large cell transformation and one died of lymphoma. Three of four patients with head and neck presentation developed extracutaneous disease. Conclusions MZCL appears to be a well recognizable entity, clinically, histologically and immunophenotypically. Although prognosis is generally good, the disease has potential for skin as well as extracutaneous recurrences. Large cell transformation and head and neck presentation may be associated with a worse prognosis.

Rosso et al recently enlarged to ten the list of patients diagnosed with yellow urticaria (YU). These cases of YU remind clinicians that the skin, besides forming a biological barrier to protect internal organs and systems from the external environment, frequently reflects underlying internal diseases. YU has been described secondary to infective hepatitis1, liver cirrhosis (regardless of the cause) 2, 3, 4, 5, 6, acute liver failure7, and metastatic disease of the liver8. This article is protected by copyright. All rights reserved.

Background: Cutaneous lymphocyte-associated antigen (CLA) is a lymphocyte homing receptor selectively expressed by T cells of the cutaneous immune system and their malignant counterpart, that is to say, cutaneous T-cell lymphomas. However it is absent in the vast mayority of other T-cell malignancies and B-cell lineage lymphomas irrespective on primary tumor site. Methods: Expression of CLA was investigated on six cases of mantle cell lymphoma (MCL) which differed in their histopathological subtype (typical or blastic) and their tendency to infiltrate skin and/or central nervous system (CNS). Results: CLA immunostaining on neoplastic cells was only observed in a 61-year-old female suffering from a lymphoblastoid MCL which clinically presented with specific skin lesions and further developped CNS disease. In this patient, coexpression of CLA with MCL markers (CD20 and CD5) was confirmed by conventional immunohistochemistry and double immunofluorescence studies. Conclusions: To our knowledge, CLA immunoreactivity on B-cell lymphomas has not beeen previously reported. The expression of this skin-related adhesion molecule on malignant MCL cells could explain the clinical behavior of our case which presented and relapsed with cutaneous lesions. However, CLA seems not to be a MCL marker nor a CNS-related adhesion molecule. The authors review the clinical and histopathological characteristics of MCL-specific skin lesions and their diagnostic clues based on cell morphology, immunohistochemistry and molecular investigations.

Background: Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. Objective: We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. Methods: Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. Results: Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. Limitations: This was a case series retrospective study. Conclusion: Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.