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Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

INTRODUCTION Small-sized pigmented lesions (SSPL)

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p

PURPOSE To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050 ). RESULTS We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. CONCLUSION The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.

Enlarging melanocytic lesions with peripheral globular pattern (EMLPGP) are a pitfall in dermoscopy. Our aim was to evaluate the meaning of EMLPGP and to assess the use of dermoscopy and reflectance confocal microscopy (RCM) in order to improve the clinical management of this subtype of melanocytic lesions.A total of 135 EMLPGP were recruited and, accordingly to the dermoscopy features, were removed; later, an expert dermoscopist reviewed the lesions blinded to histology. Moreover, a subgroup of 63 lesions who underwent also to RCM, were reviewed by an expert confocalist.Patients had a median age of 41 years old and a female prevalence (61.5%). The main anatomic site was the trunk (86%). Histology of the 135 excised EMLPGP disclosed 116 nevi (86%; P0.0001) and 19 melanomas (14%). On dermoscopy, statistical significance was detected for small globules that were observed in 106 cases (78.5%; P0.0001), while globules distribution and color did not impact the diagnosis prediction, as well as age, sex or any other patient profile. Considering the RCM, atypical cytology and irregular architecture were detected in 100% of melanomas (P0.0001).Our study shows that EMLPGPs are detectable in every age and can be a pitfall in especially in high risk patients with an over-excision of lesions. The presence of peripheral globules should be evaluated considering the overall dermoscopic features. RCM can contribute significantly in the management of lesions trough the detection of cyto-architectural atypia. Therefore, RCM in combination with dermoscopy can optimize the reduction of harmless lesions.

Background. Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. CMM pathogenesis involves genetic and environmental factors. Recent studies have led to the identification of new genes involved in CMM susceptibility: beyond CDKN2A and CDK4, BAP1, POT1, and MITF were recently identified as potential high-risk melanoma susceptibility genes. Objective: This study is aimed to evaluate the genetic predisposition to CMM in patients from central Italy. Methods: From 1998 to 2017, genetic testing was performed in 888 cases with multiple primary melanoma and/or familial melanoma. Genetic analyses included the sequencing CDKN2A, CDK4, BAP1, POT1, and MITF in 202 cases, and of only CDKN2A and CDK4 codon 24 in 686 patients. By the evaluation of the personal and familial history, patients were divided in two clinical categories: “low significance” and “high significance” cases. Results: 128 patients (72% belonging to the “high significance” category, 28% belonging to the “low significance” category) were found to carry a DNA change defined as pathogenic, likely pathogenic, variant of unknown significance (VUS)-favoring pathogenic or VUS. Conclusions: It is important to verify the genetic predisposition in CMM patients for an early diagnosis of further melanomas and/or other tumors associated with the characterized genotype.

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.6 years, 57% have been treated. As initial therapy 79% of patients received chemo-immunotherapy, 13% a chemo-free induction and 8% chemotherapy only. At relapse or progression, 6% underwent an autologous stem cell transplantation. Overall, 19% of patients received ibrutinib during the course of the disease. According to IPSSWM, 63% were classified as low risk, 27% as intermediate risk and 10% as high risk. Five-year OS was shorter in high-risk as compared with low or intermediate risk patients (92.9% vs 100% P = .002). According to revised IPSSWM, 92% were classified as very low or low risk and 8% as intermediate risk, with a shorter 5-year OS in the latter group (87.5% vs 100%, P = .028). The OS of young WM patients was not significantly reduced as compared with age-matched, sex-matched and calendar year-matched general population. Early diagnosis, absence of high-risk features in symptomatic patients and high efficacy of modern treatments are the main determinants of the excellent outcome of young WM patients.

International audience; Background: International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported.Subjects, materials, and methods: We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort [ConC]: n = 9) or subsequently (sequential cohort [SeqC]: n = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like).Results: Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in SeqC, compared to only one patient in ConC. At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%).Conclusion: Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity.Implications for practice: Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT.

Background and objectives A cross-sectional biomonitoring study was performed in Modena (Italy) to assess trace element levels in toenails in a population living near a municipal solid waste incinerator (SWI), and investigate potential differences in their concentrations according to SWI emission exposure and other environmental and behavioral factors. Methods During the winter 2013/14 eligible subjects, aged 18–69 yrs, living within 4 km from SWI, were randomly selected from the population register. Toxic and essential element concentrations (As, Cd, Cr, Cu, Mn, Ni, Pb, Se, Zn) were analyzed in 489 toenail samples. Individual exposure to SWI emissions was estimated by using, as a tracer, fall-out maps of emitted particulate matter. Information on anthropometric parameters, lifestyles, diet, and road traffic, residential and work exposures were collected by questionnaires and objective measurements. Multivariate logistic regression analyses were carried out, separately for females and males. Results Excluding As, toxic elements were found, usually at low levels, in many samples, while essential elements, especially Cu and Zn, showed higher levels. Overall, no clear relationships between element levels and SWI exposure were observed, whereas associations with other environmental and lifestyle factors were found, including local food consumption, smoking and occupation. Conclusions The low pollutant concentrations measured in SWI emissions could explain the absence of clear patterns in toenail levels across SWI exposure levels. The associations observed with other factors suggest that, at least in this specific population, other environmental exposures and personal behaviors could act as more important predictors of trace element uptake.

Background and objectives Malignant lymphomas are cancers of the immune system and are characterized by enlarged lymph nodes that typically spread across many different sites. Many different histological subtypes exist, whose diagnosis is typically based on sampling (biopsy) of a single tumor site, whereas total body examinations with computed tomography and positron emission tomography, though not diagnostic, are able to provide a comprehensive picture of the patient. In this work, we exploit a data-driven approach based on multiple-instance learning algorithms and texture analysis features extracted from positron emission tomography, to predict differential diagnosis of the main malignant lymphomas subtypes. Methods We exploit a multiple-instance learning setting where support vector machines and random forests are used as classifiers both at the level of single VOIs (instances) and at the level of patients (bags). We present results on two datasets comprising patients that suffer from four different types of malignant lymphomas, namely diffuse large B cell lymphoma, follicular lymphoma, Hodgkin’s lymphoma, and mantle cell lymphoma. Results Despite the complexity of the task, experimental results show that, with sufficient data samples, some cancer subtypes, such as the Hodgkin’s lymphoma, can be identified from texture information: in particular, we achieve a 97.0% of sensitivity (recall) and a 94.1% of predictive positive value (precision) on a dataset that consists in 60 patients. Conclusions The presented study indicates that texture analysis features extracted from positron emission tomography, combined with multiple-instance machine learning algorithms, can be discriminating for different malignant lymphomas subtypes.

Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post-transformation outcome of 176 biopsy-proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five-year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5-year progression-free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre-transformation treatment lines and a short time-to-transformation.

Background Actinic keratosis (AK) is a photo-induced skin lesion. It has been considered by several authors as in-situ squamous cell carcinoma (SCC), that can evolve to invasive SCC (iSCC). Given the malignant potential and because it is impossible predict which AK will evolve in iSCC, it is necessary to treat each lesion. Multiple therapeutic approaches have been described to treat AKs. In addition to the topical drugs, photodynamic therapy (PDT) has become an established therapeutic modality for grade I and II of AKs of face and scalp. Recently the daylight photo-dynamic therapy (DL-PDT) has found extensive use in the care of the AK and in the field cancerization. Methods The study included 101 patients, 90 males and 11 females, mean age 71, phototype I-II, with multiple AK I and II of the face and the scalp, treated with DL-PDT. Patients were clinically evaluated for 3 months. The aim of this study was to show our experience in Daylight Photodynamic Therapy, to confirm the validity in term of efficacy and safety of DL-PDT for I and II AK of face and scalp and to underline the patient's higher satisfaction for this type of treatment and his availability to be retreated with the DL-PDT. Results The efficacy was complete in 16 patients (15.8%), in 71 patients (70.3%) was much improved or improved and only in 14 (13.9%) subjects were minimal, while nobody had worsened or changed. The majority of patients (84.2%) patients were satisfied of the efficacy as well of the cosmetic results, only 15 (14.9%) were low satisfied and one patient was not satisfied. Conclusions This study confirms that the DL-PDT is a good alternative to c-PDT for the treatment of grade I and II AK of the face and scalp and in Rome, as in Southern Europe, it is possible to perform the DL-PDT in almost every month of year.

The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76 years). Median baseline left ventricular ejection fraction (LVEF) was 60%. Ischemic cardiopathy was the most frequent preexisting cardiac disorder (35%), followed by atrial fibrillation (15%), left ventricular hypertrophy (13%), and baseline LVEF

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy.

This study provides the dietary intakes of six trace elements (cadmium, chromium, copper, manganese, selenium and zinc), generally characterized by both nutritional and toxicological features depending on their exposure. Being diet the most relevant source of exposure to trace elements in non-professionally exposed subjects, we measured content of these trace elements in foods composing the typical Italian diet using inductively coupled plasma-mass spectrometry, and assessing dietary habits using a validated semi-quantitative food frequency questionnaire we eventually estimated dietary daily intake of trace elements in a Northern Italian community. In the 890 analyzed food samples, the main contributors to cadmium intake are cereals, vegetables and sweets, while cereals, beverages and vegetable are to primary source of manganese. The primary contributors for copper are cereals, fresh fruits and vegetables, while for chromium are beverages, cereals and meat. The main source of selenium intake are cereals and meat, followed by fish, seafood and milk and dairy products, while of zinc intake are meat, cereals, milk and dairy products. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 5.00 (3.17-7.65), 56.70 (36.08-86.70) and 66.53 (40.04-101.32) μg/day for cadmium, chromium and selenium, and corresponding figures are 0.98 (0.61-1.49), 2.34 (1.46-3.52) and 8.50 (5.21-12.48) mg/day for copper, manganese and zinc. The estimated intakes are generally within the average intake reported in other European populations, and in such cases well above the daily dietary intakes recommended by national international agencies, avoiding the risk of excess or deficiency. The present estimated intake data can be used to examine a specific trace element of interest and would afford enhanced health protection from those trace elements characterized by both nutritional and toxicological effects.

Plasmablastic lymphoma (PBL) is an uncommon, aggressive B-cell lymphoma mostly occurring in the oral cavity of human immunodeficiency virus (HIV) positive patients, but also described in extraoral sites and in HIV negative patients. One of the relatively common extraoral sites of PBL is the gastrointestinal (GI) tract. Few cases of PBL have been reported in association with inflammatory bowel disease (IBD). Here, we describe the unique presentation of a PBL involving the large bowel superficially along its entire length and without forming a tumor mass in an HIV negative patient with a recent diagnosis of ulcerative colitis.

Several studies have demonstrated the prognostic value of neutrophil‐lymphocyte ratio (NLR) in patients with solid tumors and non–Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)‐cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression‐free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression‐free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS‐cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS‐cHL patients.

Background/Objectives The clinical and dermoscopic differential diagnosis of flat pigmented facial lesions represents a great challenge for the clinicians. Our aim was to report a quantitative method based on dermoscopic features to better classify pigmented facial lesions. Methods This is a retrospective case-series study that analysed the dermoscopic features of 582 pigmented facial lesions. Results The individual patient probability of lentigo maligna (LM) was predicted by a multivariate model, with an accuracy of 0.72. According to the odds ratio at the multivariate analysis, an individual scoring index was assigned to each criterion, and a value of 4.56 was identified as optimal cut-off point. Up to a score of 2.5, the probability that a lesion is an LM is 0. The probability increases from 10 to 50% for a score ranging between 4.5 and 6. It is about 90% for a score of 7. Conclusion The optimal cut-off point obtained and the curve that identifies the probability of a patient having a LM could improve the classification and the management strategies of equivocal pigmented facial lesions.

Background Several studies have shown that professional drivers are at risk of developing work-related stress. Stress may be responsible for a variety of adverse effects and may also be associated with an increased number of accidents. Objective Perform an integrated, objective and subjective evaluation of work-related stress in bus drivers, that also considered the role of personality traits. Methods Salivary α-amylase and cortisol were measured in 42 bus drivers. Subjective stress evaluation was performed with the Perceived Stress Scale (PSS-10) and Driver Stress Inventory (DSI). To evaluate personality traits, we administered the Eysenck Personality Questionnaire-Revised (EPQ-R) and the Impulsivity Inventory (IVE). Results Salivary biomarkers showed no associations with PSS-10 and personality traits. Cortisol levels were positively correlated with fatigue (r = 0.44) at the middle of the work-shift and with aggression (r = 0.51) at the end of a day off. At the end of the work-shift, cortisol levels were negatively correlated with hazard monitoring (r = -0.37) and salivary α-amylase was positively correlated with thrill-seeking (r = 0.36). Neuroticism (β= 0.44) and impulsiveness (β= 0.38) were predictors of perceived stress by multiple regression. Conclusions An integrated method, considering both objective and subjective indicators, seems adequate to evaluate work-related stress in professional drivers. Personality traits are relevant in determining perception of stress.

In 2003 the Fondazione Italiana Linfomi (FIL) started a clinical research program for investigating initial treatment of frail elderly patients with diffuse large B-cell lymphoma (DLBCL) identified by Comprehensive Geriatric Assessment (CGA). From 2003 to 2006, 334 elderly patients underwent CGA assessment, and 99 patients were classified as frail. Frail patients had a median age of 78 years, stage III-IV disease in 62% and age-adjusted International Prognostic Index (aaIPI) of 2-3 in 53%. Treatment consisted of several different regimens according to physician discretion. After a median follow-up of 36 months, 5-year overall survival (OS) was 28%. In multivariate analysis, aaIPI 2-3 (p = 0.005) and the presence of respiratory comorbidity (p = 0.044) were the only factors that showed independent correlation with OS. Frail patients had a poorer outcome compared with fit patients also if they were treated with rituximab-containing combination chemotherapy (hazard ratio 2.37, 95% confidence interval 1.48-3.78; p < 0.001). CGA is a valid tool to prospectively identify frail subjects among elderly patients with DLBCL.

The relation between toxicity and essentiality of selenium(Se) is of growing interest in human health, as the effects may widely differ depending of its different chemical species and the exposure levels. Toenail Se has been proposed as a reliable biomarker of long-term Se exposure, but few studies investigated the correlation between its toenail content and environmental determinants(i.e.,dietary food intake). We aimed to determine the relation of toenail Se levels with serum Se species as well as food items. We recruited a random sample of Modena(Northern Italy) municipal residents, from whom we collected detailed personal information, dietary habits, toenail specimen for Se determination and a blood sample for serum Se speciation analysis. Toenail Se mean value was 0.96µg/g(range,0.47‑1.60), with slightly higher levels in females, in non-obese subjects and in Se supplements users, while it was lower in current smokers. Toenail Se positively correlated with organic Se forms, mainly selenoproteinP and selenocysteine, and inversely with the inorganic forms (selenite and selenate). Toenail Se was not associated with meat, cereals and dairy products consumption, positively correlated with fruit and slightly with vegetable intake, and negatively with fish and seafood consumption. Finally, no clear association emerged with estimated air Se exposure.

The aim of this study was to investigate the concentrations of five essential (Fe, Mn, Zn, Cu and Se) and four non-essential/toxic elements (Cr, Cd, Ni and Pb) in 35 different starter infant formulas (0-6 months) sold in Italy. In addition, a safety assessment of these trace elements was carried out, by comparing the estimated daily intake (EDI) with the adequate intake (AI) and the provisional tolerable daily intake (PTDI), with a view to provide information on the metal distribution patterns and health risk to infants arising from the consumption of these products. The concentrations were determined by using inductively coupled plasma mass spectrometry after microwave digestion. The concentrations expressed in geometric mean ± geometric standard deviation of Fe (6.17 ± 1.61 mg/L), Zn (6.21 ± 1.31 mg/L), Cu (416.4 ± 1.21 μg/L), Mn (121.5 ± 1.85 μg/L) and Se (13.27 ± 1.67 μg/L) were within legal limits. In spite of this, the mean EDIs of Fe (4.81 mg/day) and Mn (94.75 μg/day) were many times higher than the recommended AI, especially for Mn. Chromium, Ni, Cd and Pb concentrations were not detectable in 11, 37, 57 and 66% of the samples, respectively. Considering the overall sample, the GM ± GSD of these elements were 4.80 ± 5.35 μg/L for Cr, 1.02 ± 11.65 μg/L for Ni, 0.21 ± 14.83 μg/L for Cd and 0.14 ± 17.13 μg/L for Pb. The mean EDIs were far below the respective PTDI. When the safety assessment was based on the 75° percentile level of each elements, all EDIs remained well below the PTDI, with the exception of Cd, whose EDI approached (74.7%), albeit remaining below the PTDI. In conclusion, our results and the increased awareness on the potential risks of excessive Mn and Fe for infants support that an urgent scientific-based definition of the appropriated levels of fortification in formulas is required. Moreover, regular monitoring of all the stages of production of infant formulas is essential in order to limit toxic metal contamination.

BACKGROUND: Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article.METHODS: For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01011920.FINDINGS: Between Feb 19, 2010, and Aug 27, 2014, 227 eligible patients were recruited. 219 of these 227 enrolled patients were assessable. At median follow-up of 30 months (IQR 22-38), patients treated with rituximab and thiotepa had a complete remission rate of 49% (95% CI 38-60), compared with 23% (14-31) of those treated with methotrexate-cytarabine alone (hazard ratio 0·46, 95% CI 0·28-0·74) and 30% (21-42) of those treated with methotrexate-cytarabine plus rituximab (0·61, 0·40-0·94). Grade 4 haematological toxicity was more frequent in patients treated with methotrexate-cytarabine plus rituximab and thiotepa, but infective complications were similar in the three groups. The most common grade 3-4 adverse events in all three groups were neutropenia, thrombocytopenia, anaemia, and febrile neutropenia or infections. 13 (6%) patients died of toxicity.INTERPRETATION: With the limitations of a randomised phase 2 study design, the IELSG32 trial provides a high level of evidence supporting the use of MATRix combination as the new standard chemoimmunotherapy for patients aged up to 70 years with newly diagnosed primary CNS lymphoma and as the control group for future randomised trials.FUNDING: Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Foundation.

Purpose The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years. Patients and Methods Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). Results The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). Conclusion With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.

We present the final results of a Phase II study that evaluated safety and efficacy of lenalidomide in combination with rituximab in 39 patients with recurrent small lymphocytic lymphoma (N=18), marginal zone lymphoma (N=8), or lymphoplasmacytic lymphoma (N=13). Patients received oral doses of lenalidomide 20 mg once daily on days 1-21 and rituximab 375 mg/m2 on day 14 of each 28-day course. Patients received up to 6 courses. The overall response was 54%, with a complete response of 21%. At 2 years, progression free survival, duration of remission, and overall survival were 45%, 76%, and 78%, respectively. The evaluation of treatment response by histology showed an overall response rates of 75%, 46%, and 50%, in marginal zone, lymphoplasmacytic and small lymphocytic lymphoma, respectively. Histology-based estimates of remission durations at 2 years were 100%, 100%, and 51% for marginal zone, lymphoplasmacytic, and small lymphocytic lymphomas, respectively. A log rank test showed that the marginal zone and lymphoplasmacytic lymphoma curves were marginally significantly different from the small lymphocytic lymphoma curve. Our results demonstrated that patients with recurrent marginal zone and lymphoplasmacytic lymphomas that responded to the combination treatment had long-lasting responses. Of note, no other studies have published the effects of this combination treatment on patients with relapsed lymphoplasmacytic lymphoma. Our findings showed a mild, predictable, and manageable toxicity profile. Confirmation of these results in Phase III trials will facilitate moving towards a chemotherapy-free approach in the management of indolent non-Hodgkin lymphoma. ClinicalTrials.gov; Identifier: [NCT01830478][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01830478&atom=%2Fhaematol%2Fearly%2F2016%2F02%2F01%2Fhaematol.2015.139329.atom

Background: Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their management is hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-γ release blood assays T-SPOT.TB (TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy for latent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown. Methods and results: Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneously performed, their results were compared, and intertest agreement was evaluated. Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p < 0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (κ = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (κ = 0.16) or QFT-IT (κ = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001). Conclusions: Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based on these results, we recommend tailoring application of the new blood IFN-γ assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.

Eccrine poroma can mimic benign and malignant melanocytic and non-melanocytic lesions. To date, little is known about the dermoscopic features of this condition. Seven histopathologically proven cases of eccrine poroma were examined using dermoscopy by three independent dermatologists. Both glomerular and hairpin vessels were observed in 71% of cases, whereas linear irregular vessels were observed in 43% of cases. A white-to-pink halo surrounding the vessels and multiple pink-white structureless areas were also frequently found (in 86% and 71% of cases, respectively). Three dermoscopic "profiles" were identified, all characterized by the presence of a white-to-pink halo surrounding the vessels, as well as by the association of two additional different features, namely: glomerular vessels and pink-white structureless areas, glomerular and linear irregular vessels, hairpin vessels and linear irregular vessels. However, due to the small number of lesions studied so far, we suggest that these profiles should be considered as likely, but not definitely pathognomonic signs of eccrine poroma.

Despite its low incidence, vulvar melanoma carries a poor prognosis and shows a high tendency to metastasize because the diagnosis is often delayed. Although it is very well known that ultraviolet radiation is an important aetiological factor for cutaneous melanomas in adults, this cannot be considered true for vulvar melanoma. Chronic inflammatory disease, viral infections, irritant agents are the main factors suspected to induce mucosal melanoma. We report 10 cases of vulvar malignant melanoma observed in our institute from 1990 to 2005 and a review of the literature.

Isolated extramedullary relapse (IEMR) is a pattern of acute myeloid leukemia (AML) relapse post-allogeneic bone marrow transplantation (alloBMT). Less is known about IEMR post-autologous BMT (autoBMT) and about factors associated with IEMR. We report a case of a woman with M4 AML who experienced IEMR post-autoBMT and review the related literature. Seventy-two alloBMT and 3 autoBMT patients, including ours, were identified. The review suggests that an M2 or M4 French-American-British (FAB) phenotype, intermediate cytogenetic risk group, and chromosome 8 abnormalities are more frequently associated with the occurrence of IEMR. IEMR occurs earlier in autoBMT than in alloBMT. Combined treatment with radiation and high-dose chemotherapy may be effective. When we searched the European Bone Marrow Transplant Registry (EBMTR) database, we found the incidence of IEMR to be statistically greater in alloBMT than in autoBMT (11% vs. 6%; P = 0.02), but no correlations have been found with the conditioning transplant regimen used. A closer follow-up, including body and central nervous system scan, should be considered in patients who are undergoing BMT presenting with several IEMR-associated factors.

Aims: To our knowledge, no randomised study has compared rates of uncovered stent struts in everolimus (EES) vs. newgeneration zotarolimuseluting (ZES-R) stents in acute coronary syndrome (ACS). The aim of our study was to evaluate the completeness of neointimal coverage with optical coherence tomography (OCT) in ACS patients treated with drug-eluting stents (DES) comparing EES versus new-generation ZES-R. Methods and results: All eligible ACS patients admitted to four Italian centres with a clinical indication for culprit lesion intervention were randomised 1:1 to EES or ZES-R. The primary study endpoint was the percentage of uncovered stent struts evaluated by optical coherence tomography (OCT) at six months. Secondary endpoints were the percentage of malapposed stent struts, percent neointimal hyperplasia crosssectional area (CSA) and major adverse cardiac events (MACE) at six months. A total of 60 patients were randomised to EES (n=29) or ZES-R (n=31). No differences were observed in baseline characteristics between the two groups. Overall, 31.7% presented with STEMI, of which 68.4% were anterior. The other patients comprised 41.7% NSTEMI and 26.7% troponin-negative ACS. A mean of 1.3±0.6 lesions were treated per patient, with a mean of 1.3±0.5 stents per lesion. At 30 days there was one sudden death. Sixmonth OCT analysis was performed in 25 lesions in the EES group and in 24 lesions in the ZES-R group. There was no difference in the primary endpoint of uncovered stent struts between groups (EES 6.42% [3.27, 9.57] vs. ZES-R 7.07% [3.22, 10.92]; p=0.80). Furthermore, there were no differences between groups in the percentage of malapposed stent struts, either with (EES 1.19% [0.34, 2.04] vs. ZES-R 0.85% [0.40, 1.30]; p=0.49) or without coverage (EES 1.06% [0.12, 2.01] vs. ZES-R 0.24% [0.05, 0.44]; p=0.09). Percent neointima CSA was similar in both groups (EES 37.0% [18.6, 55.3] vs. ZES-R 26.6% [18.4, 34.8]; p=0.31). At sixmonth clinical followup, no additional patients died or suffered MI. There were four MACE in the EES group and one in the ZES-R group. Conclusions: In our study, in patients presenting with ACS, both EES and ZES-R had low percentages of malapposed and uncovered stent struts at sixmonth OCT analysis.

Background A combined nevus most commonly consists of a blue nevus in combination with a Clark or Spitz nevus. Dermoscopically, combined nevus can mimic melanoma owing to the presence of dermoscopic features common to both types of lesions. Benign clinical and dermoscopic changes can occur in nevi over time, especially in children and young adults. Objective To describe the dermoscopic evolution of a congenital combined nevus showing unusual dermoscopic features. Methods Digital dermoscopic analysis was performed at the initial visit and after 8 months. The lesion was surgically excised and histopathologically examined. Results An asymptomatic plaque with a central blue area and peripheral brown pigmentation located on the back of a 13-year-old boy was diagnosed dermoscopically as combined nevus. Dermoscopic analysis 8 months later showed color changes from steel blue to gray-blue and black in the central area of the lesion, an increased number of blue-black dots or globules, and peripheral irregular streaks. Histopathology revealed typical features of a congenital combined nevus (blue nevus + compound nevus). Conclusion Over time, congenital combined nevus may show clinical and dermoscopic changes in size, color, and structure. Surgical excision is recommended when clinical and dermoscopic features are equivocal and the diagnosis of melanoma cannot be ruled out.

We assessed the prognostic value of minimal residual disease (MRD) within the ML17638 phase 3 trial from the Fondazione Italiana Linfomi, investigating the role of rituximab maintenance in elderly follicular lymphoma (FL) patients after a brief first-line chemoimmunotherapy. MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to the Euro-MRD consortium, using qualitative and quantitative polymerase chain reactions (PCRs). Of 234 enrolled patients, 227 (97%) were screened at diagnosis. A molecular marker (MM) was found in 51%. Patients with an MM were monitored at 8 subsequent times. Of the 675 expected follow-up samples, 83% were analyzed. Conversion to PCR negativity predicted better progression-free survival (PFS) at all post-treatment times (eg, end of therapy: 3-year PFS, 72% vs 39%; P < .007). MRD was predictive in both maintenance (83% vs 60%; P < .007) and observation (71% vs 50%; P < .001) groups. PCR positivity at the end of induction was an independent adverse predictor (hazard ratio, 3.1; 95% confidence interval, 1.36-7.07). MRD is a powerful independent outcome predictor in FL patients who receive rituximab-intensive programs, suggesting a need to investigate its value for decision-making. This trial was registered at www.clinicaltrial.gov as #NCT01144364.

While the histological epidermal criteria (psoriasiform acanthosis, pale-appearing keratinocytes, parakeratosis, and neutrophilic exocytosis) of clear cell acanthoma (CCA) are usually well known,1 the dermal ones have been less investigated. We attempted to evaluate the frequency of vascular and eccrine findings in CCA and to correlate them with dermoscopy (Fig 1 and Supplemental Fig 1 [available at http://www.jaad.org]).

Aims and background A direct association between exposure to the metalloid selenium and risk of cutaneous melanoma has been suggested by some observational and experimental cohort studies, whereas other studies have yielded inconsistent results. Since some of the inconsistencies may be due to exposure misclassification arising from the use of exposure indicators that do not adequately reflect body tissue selenium content or the levels of the biologically relevant species of this metalloid, we examined this issue using multiple indicators of exposure. Methods We analyzed the relation of selenium exposure with risk of cutaneous melanoma using two different biomarkers, plasma and toenail selenium concentration, and estimated dietary selenium intake in a population-based case-control series (54 cases, 56 controls) from an Italian community. Results In unmatched and matched logistic regression models as well as nonparametric generalized additive models, higher plasma selenium levels were strongly associated with excess disease risk. In contrast, toenail and dietary selenium exhibited little relation with melanoma risk. The pattern of correlation among indicators of exposure differed by disease status, with dietary intake associated with plasma selenium levels in patients but not in controls. Conclusions Our data showed that different selenium exposure indicators can yield different inferences about melanoma risk. Although the series was small, our results are consistent with a positive association between circulating levels of selenium and melanoma risk. Further investigation of the exposure classification performance of various selenium biomarkers and of metabolic patterns of the metalloid and of its speciation are needed to help elucidate the relation between selenium exposure and human health.

background. A dermoscopic method based on the absence of a pigment network and the presence of at least one of six positive features has been described for diagnosis of pigmented basal cell carcinoma (BCC). objective. To evaluate the observers' global agreement and interobserver agreement on each dermoscopic parameter of the method recently proposed. methods. Dermoscopic images of 56 pigmented BCCs were examined by five observers with different degrees of experience in dermoscopy. results. An overall full agreement was reached for the absence of pigment network (k = 1). Very good agreement was detected for the presence of spoke wheel areas (k = 0.85) and arborizing vessels (k = 0.72), and good agreement was shown for ulceration (k = 0.49) and multiple blue-gray globules (k = 0.41). No agreement was identified on large blue-gray ovoid nests (k = 0.28) and leaflike areas (k = 0.26). conclusion. We confirm the reproducibility of the method and show that ulceration, spoke wheel areas, and arborizing tel- angiectases represent the most robust positive parameters.

Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100d post-transplant in 195 consecutive adult recipients of a reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-allo).The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia.FN occurred in 141 patients (72%), always in the first 30d post-allo-RIC. However, a SBI occurred in only 27 patients (14%) during this early post-transplant period (day +30), while 29 evaluable patients (15%) developed a SBI in the intermediate post-transplant period (days +31 to +100). In multivariate analysis, RFs for the development of FN included onset of neutropenia before day +5 after allo-RIC (P0.02) and NCI CTC grade III-IV mucosal damage in the first 10d post-transplantation (P=0.03). RFs identified to SBI by multivariate analysis included corticosteroid therapy before day +100 (P0.01), mycophenolate mofetil-based graft-versus-host disease (GVHD) prophylaxis (P0.01), and previous SBI before day +30 (P0.01). The rate of SBI from day +30 to +100 varied according to the number of RFs; thus, the rate of SBI was 1% in patients without any RF, 17% in patients with one RF, 29% with one RFs, and 53% in those with all three RFs.After an RIC-allo, FN and early SBI occurred mostly in patients with severe mucositis and early-onset neutropenia, while postengraftment high-dose steroid therapy for acute GVHD was the major RF.

Cardiac stem cell therapy is a field of scientific research with the goal to translate into clinical benefit the initial findings obtained in basic research laboratories. We have moved into clinical trials in different disease categories: acute myocardial infarction, chronic stable angina refractory to conventional therapy and heart failure. So far we have faced with contradictory results. Some previous studies suggested that bone marrow cell injection may improve myocardial perfusion and left ventricular function in patients with chronic myocardial ischemia.In this paper we present a brief review about stem cell use in clinical cardiology and describe our research protocol evaluating the effects of direct intramyocardial injection of autologous bone marrow cells (CD34+ selected cells versus all mononuclear cells) in patients with chronic myocardial ischemia.Preliminary results show that this procedure seems to be safe and generally well tolerated by patients. An improvement in symptoms, in the first 6 months, appears to be achieved in approximately 50% of patients, with concomitant improvement of quantitative scintigraphic stress test imaging.Before drawing any definitive conclusions, we need to wait for the end of enrollment and unblinding of study randomization.

Acute promyelocytic leukaemia (APL) is a unique clinicobiologic entity that can be successfully treated with All-trans Retinoic Acid ATRA-based regimens. Some cases of acute myeloid leukaemia (AML) with nucleophosmin (NPM) mutations have an immunophenotype that is similar to APL. The objective of the study is to compare antigenic expression in a group of APL patients with that in AML patients with NPM mutations and an APL-like immunophenotype (CD15- CD34- HLA-DR-). A consecutive series of 40 APL and 12 NPM patients with an APL-like phenotype were included in the study. Immunophenotypic patterns were investigated by multiparametric flow cytometry. Promyelocytic leukaemia-retinoic acid receptor-α transcript type, NPM and FLT3 mutations were investigated using conventional methods. Statistically significant differences were found between APL and NPM-mutated AML in CD33, CD13, CD2 and CD110 reactivity. CD2 expression was absent in every patient with NPM-mutated AML. In addition, mean fluorescence intensity and the coefficient of variation (cv) of CD33 and CD13 showed statistical differences between the two groups for CD33 (p = 0.007) and a trend to significance for CD13 (p = 0.05). Furthermore, among 45 evaluable patients, CD110 expression statistically differentiates between the two groups: [2/33 (6%) in the APL group and 8/12 (66.6%) in the NPM-mutated AML (p = 0.014)]. However, these traits were subtle, raising the possibility of practical diagnostic challenges. In conclusion, CD110 and CD33 reactivity may be useful to distinguish APL from NPM-mutated AML with CD15, CD34 and HLA-DR negativity. Nevertheless, cytogenetic and molecular characterization is necessary to establish the accurate diagnosis of AML.

CDKN2A is the most common, most penetrant gene whom germline mutations predisposing to cutaneous familial melanoma (FAM). Multiple primary melanoma (MPM), early age at onset, >2 affected members and pancreatic cancer are consistent features predicting positive test. However, the impact that cumulative clinical features have on the likelihood of molecular testing is unknown. In this work, genotype–phenotype correlations focused on selected clinical features were performed in 100 Italian FAM unrelated patients. Molecular studies of CDKN2A mutations were performed by direct sequencing. Statistical study included multiple correspondence analysis, uni- and multivariate analyses, and individual patient's probability calculation. MPM, >2 affected family members, Breslow thickness >0.4mm, and age at onset ≤41 years were the unique independent features predicting positive CDKN2A screening. The rate of positive testing ranged from 93.2% in the presence of all of them, to 0.4% in their absence. The contribution of each of them was quantified accordingly, with MPM being the most significant. These findings confirm previous data and add novel insights for the role of accurate patients' selection in CDKN2A screening.

Background: The dermoscopic patterns of pigmented skin tumors are influenced by the body site. Objective: To evaluate the clinical and dermoscopic features associated with pigmented vulvar lesions. Methods: Retrospective analysis of clinical and dermoscopic images of vulvar lesions. The χ2 test was used to test the association between clinical data and histopathological diagnosis. Results: A total of 42 (32.8%) melanocytic and 86 (67.2%) nonmelanocytic vulvar lesions were analyzed. Nevi significantly prevailed in younger women compared with melanomas and melanosis and exhibited most commonly a globular/cobblestone (51.3%) and a mixed (21.6%) pattern. Dermoscopically all melanomas showed a multicomponent pattern. Melanotic macules showed clinical overlapping features with melanoma, but their dermoscopic patterns differed significantly from those observed in melanomas. Conclusion: The diagnosis and management of pigmented vulvar lesions should be based on a good clinicodermoscopic correlation. Dermoscopy may be helpful in the differentiation of solitary melanotic macules from early melanoma.

CONFOCAL REFLECTANCE MICROSCOPY Confocal reflectance microscopic examination was performed with the handled Vivascope 3000 (Caliber Imaging and Diagnostics, Inc, Rochester, NY). A regular honeycomb pattern was detected in the superficial layers. At the level of the epithelialechorion junction, cord-like structures were visible, and these were composed of tubular structures rimmed by monomorphic roundish cells that corresponded to the parallel pattern seen during the dermoscopic evaluation (Fig 2, A [maroon square] and B). In the area of the dermoscopic ring-like pattern, dermal papillae appeared rimmed by bright, monomorphic, roundish cells, corresponding to hyperpigmented keratinocytes (Fig 2, A [blue square] and C ). A few plump, bright cells corresponding tomelanophages were seenwithin the dermal papillae (Fig 2, C ).