Malignant perivascular epithelioid cell tumor in children: description of a case and review of the literature.

Perivascular epithelioid cell tumors (PEComas) include different morphological entities originating from perivascular epitheliod cells. Their clinical behavior is not predictable, and there are no strict histologic criteria for malignancy, although larger tumors with infiltrative growth, hypercellularity, cellular atypia, atypical mitoses, and necrosis generally have a malignant course. Pediatric PEComas are rare, with less than 40 cases reported, mostly in children older than 5 years. We describe a case of malignant PEComa of the ligamentum teres in a 2-year-old girl, characterized by the occurrence of local relapse after primary treatment with chemotherapy and surgery and poor response to imatinib mesilate and temsirolimus used after further analyses confirmed p70S6K expression involved in the mTOR pathway. The girl was eventually treated with a debulking surgical procedure and is now alive with disease 6 years after diagnosis. Literature data of children affected by PEComas were also analyzed, trying to identify pathologic characteristics that could predict their course and therapeutic options. Histologically, they may be differentiated in 3 prognostic categories: (1) benign, lacking unfavorable morphological markers; (2) with uncertain malignant potential, carrying 1 unfavorable marker; and (3) malignant, with at least 2 unfavorable markers. In the literature, 9% of cases occurred as a second malignancy probably because of genomic instability related to treatment. Their different biology and the potential value of targeted therapies remain to be explored. The indolent evolution in our patient was similar to that reported in some other cases in the literature. In terms of treatment, the present case suggests a minor response to temsirolimus compared with the adult population

CARATTERISTICHE E SOPRAVVIVENZA DEI PAZIENTI DI ET\uc0 INFERIORE AI 2 ANNI AFFETTI DA LINFOMA NON HODGKIN (LNH) TRATTATI CON I PROTOCOLLI MULTICENTRICI AIEOP LNH-92 E 97

Introduzione ed obiettivi. Recentemente \ue8 stato segnalato che gli Infants affetti da LNH, in confronto al gruppo di bambini di et\ue0>24 mesi alla diagnosi, hanno una prognosi peggiore in termini di probabilit\ue0 di sopravvivenza globale (pOS) e libera da malattia (pEFS), in linea con quanto gi\ue0 osservato per la leucemia acuta. Qui riportiamo la prevalenza, le caratteristiche cliniche e i risultati del trattamento degli Infants trattati nei due protocolli nazionali AIEOP LNH-92 e 97. Metodi. Dal 10/1992 al 12/2005, 641 pazienti (pts) eleggibili sono stati trattati nei protocolli AIEOP LNH-92 e 97. Di questi, 13 (2%) sono Infants: 3 (23%) con LNH linfoblastico T maturo (T-LBL), 2 (15%) con LBL pre-B (pB-LBL), 7 (54%) con LNH B maturo (B-LNH) e 1 (8%) con LNH a grandi cellule B; nessun pts con ALCL. Di questi, 6 erano M e 7 F (M/F=1:1.2); et\ue0 mediana alla diagnosi 15 (0.8-22.6) mesi e tempo mediano di osservazione 6.8 (1.5-15) anni. Stadio secondo St. Jude: 1/I, 3/II, 6/III e 3/IV SNC-. Sedi coinvolte alla diagnosi: mediastino (n=3), addome (n=4), cute (n=2), anello di Waldeyer (n=2), noduli sottocutanei (n=1), fegato e reni (n=1). Il midollo osseo (BM) era coinvolto in 3 pts, mentre nessuno presentava coinvolgimento al SNC. Nessun paziente ha mostrato anomalie costituzionali; in 1 paziente con B-NHL la traslocazione t(8;14) \ue8 risultata positiva mediante LD-PCR, sia su biopsia linfonodale che su BM. I pts con T e pB-LBL sono stati trattati con terapia di durata di 24 mesi, mentre i pts con B-LNH hanno ricevuto da 2 a 6 cicli ad alta-dose-intensit\ue0. Risultati. Tutti i pazienti hanno ottenuto la RC. Due sono recidivati: il primo, pB-LBL, recidivato nel BM a 20 mesi dalla diagnosi, trattato con REC 98 e alloTMO, \ue8 vivo in II RC; il secondo, B-LNH a grandi cellule, ricaduto in sede testicolare a 19 mesi dalla diagnosi, trattato con protocollo per pB-LBL, \ue8 vivo in II RC. Nessuno \ue8 deceduto n\ue9 ha presentato tossicit\ue0 maggiori. La pOS e la pEFS a 8 anni degli Infants, rispetto ai bambini pi\uf9 grandi trattati nello stesso periodo, sono rispettivamente 100% vs. 83.8+2% (p=0.159) e 83.3+10% vs. 78.4+2% (p=0.582). Conclusioni. I nostri dati preliminari suggeriscono che gli Infants con LNH hanno una prognosi sovrapponibile, sia in termini di pOS che di pEFS, a quella dei bambini >24 mesi. Questi dati si discostano da quelli riportati da altri gruppi internazionali

Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry

BACKGROUND: The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. DESIGN AND METHODS: We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. RESULTS: During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51-0.61) and 0.70 (95% CI: 0.65-0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53-0.62) overall, and 1.08 (95% CI: 0.99-1.17) when analyses were restricted to married/cohabiting women CONCLUSIONS: Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood

Patterns of domestic migrations and access to childhood cancer care centres in Italy: a report from the hospital based registry of the Italian Association of Pediatric Hematology and Oncology (AIEOP).

Tertiary care centres, grouped in the Italian Association of Paediatric Haematology and Oncology (AIEOP) are unevenly distributed across the country. In an attempt to describe their perceived efficacy, we matched the residence and the location of the treatment centre in 18,441 patients aged <or=15 years treated in the AIEOP network between 1989 and 2005. Overall, centres located in the central and southern regions were less appealing than those located in the North, although this trend decreased over the study period. Patients with solid tumours migrated more frequently than those with leukaemia or lymphoma. Information resulting from better knowledge of the non-random migrations for treatment of children with cancer will be useful to refine planning of the national paediatric haematology-oncology network with social and economic implications

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group \u2013 KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients\u2019 outcome were collected in an online anonymized database (RedCAP\uae). Relationship between clinical presentation and SARSCoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS \u201cBurlo Garofolo\u201d, Trieste; AOU Meyer, Florence;IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/ non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71, 9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p &lt; 0.0001). SARSCoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p &lt; 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility: evidence from a Nationwide Italian Twin Study.

CONTEXT: The incidence of type 1 diabetes has been increasing over time. OBJECTIVE: We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of recent-onset cases to explore the sources of changing disease epidemiology. DESIGN: We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire. OUTCOME MEASURES: We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models. RESULTS: We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1-20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8-78), and the shared and individual-specific environmental components were 51% (14-77) and 9% (4-19), respectively. CONCLUSIONS: In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease

Italian cancer figures, report 2012: Cancer in children and adolescents.

OBJECTIVES: This study describes up-to-date cancer incidence and survival in Italian paediatric and adolescent patients, based on data collected by the network of Italian cancer registries (AIRTUM). It updates the monograph published on the same topic in 2008. The main objective of this monograph is to present the statistics according to standard rigorous epidemiological methods and disseminate them to a wide range of readers, including the lay public. Given the deep impact of the 2008 monograph on the general public, in this update we complement descriptive statistics with additional data and commentaries on issues of importance for public health, in order to provide unambiguous criteria on how to interpret the statistics. The study is the result of the collaboration between AIRTUM and AIEOP (Italian Association of Paediatric Haematology and Oncology) with contributions from interested parties, including representatives of parent associations. The monograph is divided into three parts. The first part presents incidence rates, survival probabilities, and time trends, by sex, age, geographical area, and cancer site or type, by means of tables and graphs as in the previous monograph, to facilitate direct comparisons. Four articles summarize and comment the results. The second part uses data from AIRTUM and AIEOP to outline patient management and health care issues; it includes estimates of the number of new cases in the next decade and of young adults living after a paediatric cancer diagnosis. Health organizational aspects of treatment services for paediatric patients, based on the AIEOP database, are also discussed, along with long-term complications in cured patients. The third section describes the changes in mortality trends due to improving therapies and healthcare services, and discusses risk factors and prevention of childhood cancer, late adverse events in cured patients, and other related issues. MATERIAL AND METHODS: Data herein presented were provided by AIRTUM population-based cancer registries, covering 47%of the Italian population below age 20 years, in the period 2003-2008. Quality of cancer registration in Italy is elevated, with high proportions of microscopically verified diagnoses (91%in the 0-14 years age group and 96% between 15 and 19 years of age) and a very small proportion of cases collected through death certificate only (0.1%).The proportion of cases in diagnostic groups XI (other malignant epithelial neoplasms) and XII (other and unspecified neoplasms) of the International Classification for Childhood Cancer (ICCC), based on the third revision of the International Classification of Diseases for Oncology (ICD-O-3), were 7.0% in the 0-14 years age group and 26.0%in the 15-19 years age group.The ratio between mortality and incidence was 17.7% in both children and adolescents. Detailed results are presented in 24 fact sheets for the 12 major ICCC-3 diagnostic groups and 10 sub-groups of special interest; the series is completed by a sheet on all malignant tumours and one on all tumours including non-malignant neoplasms of the central nervous system. All sheets include results for three age groups (0-14, 15-19, and 0-19 years) and are followed by two commentaries on incidence in the recent period, one on trends and the other on survival. Incidence rates were age-standardized on the European population and presented per million children. Incidence rates are also presented by age group, sex, and geographical area. Incidence trends were evaluated for two periods, 1988-2008 and 1998-2008, using estimated annual percent changes, and survival estimates were calculated by age and period. Indicators and corresponding 95% confidence intervals are shown in forms of graphics and tables at the end of the monograph and online at http://www.registri-tumori.it. Geographical analyses were conducted rearranging cancer registries into four macroareas (North-West, North-East, Centre, and South and Islands). Age groups were the same used in descriptive studies on children worldwide (0, 1-4, 5-9, 10- 14 years for paediatric tumours and 15-19 years for adolescents). Incidence trend analyses included cancer registries with three or more years of registration in the 5-year period, using Poisson regression models. Observed survival was computed according to the Kaplan-Meier method. The estimate of expected cases in the next decade was based on observed incidence rates in the most recent period, extended to the Italian estimated population of children and adolescents in the periods 2011-2015 and 2016-2020. The AIEOP database (Modello 1.01) allowed us to compare the number of patients treated and followed-up in specialized centres with expected cases based on AIRTUM estimates. The AIEOP database also provided information regarding health care migration throughout Italian regions and the number of foreign (immigrated) children treated in Italian AIEOP centres. RESULTS: In the period 2003-2008, 31 cancer registries reported 4,473 incident malignant neoplasms, 2,855 in children and 1,618 in adolescents. Cancer incidence rates were 164 cases per million in children aged 14 years or below and 269 cases per million in patients aged 15-19 years. Limited geographical variations emerged. In children (0-14 years) a significant increase in malignant cancer incidence was observed until 1997 (APC: +3.2%), followed by a plateau (APC: -1.1%not statistically significant).Until the late Nineties, a statistically significant increase was also observed in the incidence of all leukaemias in males (APC: +5.7%), lymphoid leukaemias (APC: +5.6%), representing 80% of all leukaemias, Hodgkin and non- Hodgkin lymphomas (APC: +6.3%). A significant decrease emerged for lymphoid leukaemia starting in 1995 (APC: -1.9%), while no substantial change in cancer incidence rates was observed in the last decade of observation for all malignant neoplasms and lymphomas. In addition, no variation emerged for malignant (according to the most recent classification) central nervous system (CNS) neoplasms, while an annual increase of 1.8% (significant) was observed in the period 1988-2008, when non-malignant tumours were included. Increases in cancer incidence were observed throughout the study period for neuroblastoma (APC: +1.9%) and epithelial tumours or melanoma (APC: +4.1%). In the period 1998-2008, in addition to lymphoid leukaemias, a significant decrease was observed for all malignant neoplasms, lymphomas in girls, CNS tumours (males and females), and renal tumours in girls, while no increases were observed in this age group. In adolescents (15-19 years) between 1988 and 2008, a significant increase in incidence rates was observed (APC: +2.0%) for all malignant neoplasms, all lymphomas (APC: +2.9%; in particular Hodgkin lymphoma, APC: +3.6%), thyroid cancer (APC: +6.1%), and melanoma (APC: +8.1%). Conversely, lymphoid leukaemia is the only neoplasm showing a long-term decrease in adolescents. Recent trends (1998-2008) confirm the long-term increases only for all malignant neoplasms in girls and thyroid cancer (APC: +7.9%, boys and girls), while a decrease in bone tumour incidence emerged in girls, albeit based only on 46 cases. Cancer mortality in children showed a persistent decrease for all neoplasms and even for more frequent cancer sites or types, and mortality rates for cancer were three-fold higher in the early Seventies than in 2008. In addition, five-year survival after cancer diagnosis increased in the last three decades and was still increasing in the period 2003- 2008, reaching 82% in children and 86% in adolescents. In the period 2008-2010, 4,488 children (0-14 years) were treated in one of the AIEOP clinical centres and we estimate, based on the above-presented incidence rates, that they represented 92% of all cancer cases in Italy. However, in adolescents, the proportion of patients treated in AIEOP centres was only 25%. A migration of patients living in the South of Italy to Central and Northern Italy emerged from AIEOP information. The expected number of cancer cases in children aged between 0 and 14 years of age is approximately 7,000 in the period 2016- 2020, while the corresponding figure for adolescents between 15 and 19 years of age is 4,000, with no relevant variation in comparison with the previous five-year period. COMMENTS: The present findings update descriptive cancer epidemiology in children and adolescents in Italy based on data provided by an extensive network of general and specialized population-based cancer registries. Data obtained from cancer registries are supplemented by additional information collected by specialized clinical AIEOP centres and mortality reports collected by the National Institute of Statistics (ISTAT). Incidence rates reported in Italy were slightly higher in comparison to other developed Countries, but relatively consistent between different Italian areas. Our results also showed that the significant increase in cancer incidence observed until the end of Nineties has halted, with the exception solely of thyroid cancer in adolescents. Efficacy of therapeutic protocols has improved constantly since the Seventies, and recent findings confirm this trend in all age groups and, in particular, for rarer tumours and cancer types that have very poor prognosis. Findings derived from cross-analysis with AIEOP data suggest that it is possible to further improve the efficiency of our healthcare system, in particular for adolescents; migration can be reduced with a more rational use of hospitals throughout Italy