Diencephalic Syndrome: Misleading Clinical Onset of Low-Grade Glioma.

BACKGROUND: Diencephalic Syndrome is an atypical early manifestation of low-grade gliomas; so, it is important to detect it in patients that experience a failure to thrive despite adequate length growth and food intake. The purpose of this article is to focus attention on this rare but potentially dangerous cause of poor weight gain or stunting in childhood. MATERIALS AND METHODS: We describe four patients with Diencephalic Syndrome and low-grade gliomas who were evaluated in our institution from January 2017 to December 2021. CASE DESCRIPTION AND RESULTS: two patients presented with suspected malabsorption, and two presented with a suspected eating disorder. In all cases, neurological symptoms appeared late, explaining the reason for the diagnostic delay, which impacts negatively on prognosis and on quality of life. Currently, patients 1 and 2 have stable disease in second-line therapy, patient 3 has stable disease post end of second-line therapy, and patient 4 has stable disease in first-line therapy. Everyone is in psychophysical rehabilitation. CONCLUSIONS: A multidisciplinary evaluation is essential in order to make an early diagnosis and improve prognosis and quality of life.

The Role of Ultrasound in the Diagnosis of Pulmonary Infection Caused by Intracellular, Fungal Pathogens and Mycobacteria: A Systematic Review.

BACKGROUND: Lung ultrasound (LUS) is a widely available technique allowing rapid bedside detection of different respiratory disorders. Its reliability in the diagnosis of community-acquired lung infection has been confirmed. However, its usefulness in identifying infections caused by specific and less common pathogens (e.g., in immunocompromised patients) is still uncertain. METHODS: This systematic review aimed to explore the most common LUS patterns in infections caused by intracellular, fungal pathogens or mycobacteria. RESULTS: We included 17 studies, reporting a total of 274 patients with M. pneumoniae, 30 with fungal infection and 213 with pulmonary tuberculosis (TB). Most of the studies on M. pneumoniae in children found a specific LUS pattern, mainly consolidated areas associated with diffuse B lines. The typical LUS pattern in TB consisted of consolidation and small subpleural nodes. Only one study on fungal disease reported LUS specific patterns (e.g., indicating "halo sign" or "reverse halo sign"). CONCLUSIONS: Considering the preliminary data, LUS appears to be a promising point-of-care tool, showing patterns of atypical pneumonia and TB which seem different from patterns characterizing common bacterial infection. The role of LUS in the diagnosis of fungal disease is still at an early stage of exploration. Large trials to investigate sonography in these lung infections are granted.

Radiotherapy quality assurance in paediatric clinical trials: first report from six QUARTET-affiliated trials.

BACKGROUND AND PURPOSE: SIOP Europe's QUARTET project launched in 2016; aiming to improve access to high-quality radiotherapy for children and adolescents treated within clinical trials across Europe. The aim of this report is to present the profile of institutions participating in six QUARTET-affiliated trials and a description of the initial individual case review (ICR) outcomes. METHODS: This is a two-part analysis. Firstly, using facility questionnaires, beam output audit certificates, and advanced technique credentialing records to create a profile of approved institutions, and secondly, collating trial records for ICRs submitted prior to 31/10/2022. Trials included are: SIOPEN HR-NBL1, SIOPEN-LINES, SIOPEN- VERITAS, SIOP-BTG HRMB, EpSSG-FaR-RMS, and SIOPEN HR-NBL2. RESULTS: By 31/10/2022, a total of 103 institutions had commenced QUARTET site approval procedures to participate in QUARTET-affiliated trials; 66 sites across 20 countries were approved. These participating institutions were often paediatric referral sites with intensity modulated radiotherapy or proton beam therapy, designated paediatric radiation oncologists, and paediatric adapted facilities and imaging protocols available. In total, 263 patient plans were submitted for ICR, 254 ICRs from 15 countries were completed. ICRs had a rejection rate of 39.8%, taking an average of 1.4 submissions until approval was achieved. Target delineation was the most frequent reason for rejection. CONCLUSION: The QUARTET facility questionnaire is a valuable tool for mapping resources, personnel, and technology available to children and adolescents receiving radiotherapy. Prospective ICR is essential for paediatric oncology clinical trials and should be prioritised to reduce protocol violations.

Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK).

Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms' tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases (p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases.

Neuroblastic tumors and neurofibromatosis type 1: A retrospective multicenter study in Italy and systematic review of the literature.

Background: Neuroblastic tumors (NBTs) are the most common extra-cranial solid tumors of childhood. Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder with a predisposition to tumors. The co-occurrence of NBTs in the setting of NF1 has been occasionally reported, suggesting a non-casual association and likely configuring a spectrum of neural crest-derived disorders. Aim of the study: To explore the occurrence of NBTs within NF1 and to report on its natural history, therapeutic strategies, and outcomes in an Italian cohort of children with NF1 and in the literature. Subjects and Methods: Study (a): a retrospective analysis of questionnaire-based data [years 1979-2017] derived from the databases of the Italian Registry for Neuroblastoma (RINB) of the Italian Society of Pediatric Onco-Haematology (AIEOP); and Study (b): a systematic review search on NF1/NB co-occurrence. Results: Study (a) identified eight children with NBTs, 0.2% of patients registered in the RINB, fulfilling the diagnostic criteria for NF1. The primary site of NBTs was abdominal in six patients. The NBTs were neuroblastoma (NB) in five patients, ganglioneuroblastoma (GNB) in one, patient, and ganglioneuroma (GN) in two. Metastatic diffusion occurred in three out of eight children. MYCN gene testing, performed in the tumors of five patients, resulted not-amplified. The major features of NF1 included the following: NF1 family history in four patients, café-au-lait spots in all, freckling in six, Lisch nodules in three, and neurofibromas in three. With regard to the outcome, four children survived three of these for the progression of NB and one for a second tumor. Study (b) identified 12 patients with NF1/NB from the years 1966-2017, and the median age at diagnosis was 27 months (range = 0-168 months). The primary site of NB was thoracic. The prevalent histotype was NB in nine patients, GNB in two, and GN in one. Eight/nine NBs were metastatic. The MYCN gene was amplified in the only studied case. The NF1 features included NF1 family history in seven patients; the major NF1 features were café-au-lait spots in nine patients, freckling in one, Lisch nodules in none, and neurofibromas in six. The outcome was good for only two children, while eight children died of neuroblastoma, at a median age of 49.5 months (range = 2.4-174 months), with a median survival time of 21.75 months after diagnosis. Conclusions: To our knowledge, this represents the first systematic study on the occurrence of NBTs in NF1. This confirms that NBs are rare per se in the setting of NF1 (0.2% of all NBs) and even if compared to the overall frequency of malignancies in NF1 (i.e., 14.7%). The male:female ratio in study (a) (0.6) was different from what was recorded in study (b) (1.5) and in line with the overall increased frequency of malignancies in females with NF1. The median ages at diagnosis of NB in either study (a) or (b) were concordant with what occurred in the NB population. In study (a) versus study (b), the frequency of metastatic diffusion was lower, likely indicating less awareness on work-ups for malignancies in old NF1 series in the literature. The outcome was much better in study (a) than in study (b), indicating that multidisciplinary treatment for NB is highly recommended.

Report of Two Cases of Pediatric IgG4-Related Lymphadenopathy (IgG4-LAD): IgG4-Related Disease (IgG4-RD) or a Distinct Clinical Pathological Entity?

IgG4-related disease (IgG4-RD) is a recently discovered immune-mediated fibroinflammatory condition, uncommon in the pediatric population, that could involve multiple organs and induce cancer-like lesions and organ damage. Its main features are multiple injuries in different sites, a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells, storiform fibrosis, and often high serological concentrations of IgG4. Autoimmune pancreatitis is the most common manifestation, mainly in adults. Two cases of IgG4-RD in children with lymph node localization of disease are reported. Localized or systemic lymph node involvement is common, but lymph node enlargement as the first and only manifestation of IgG4-RD is unusual, and therefore, hard to differentiate from other diseases. IgG4-related lymphadenopathy (IgG4-LAD) is most likely a distinct disease, described as isolated lymphadenopathy, related to the presence of elevated numbers of IgG4-positive plasma cells. Both disorders are likely to be misdiagnosed in children because they are characterized by rare and polymorphic features. IgG4-RD and IgG4-LAD should be considered in the differential diagnosis of disorders characterized by lymphadenopathy of uncertain etiology.

Suprarenal Masses in Very Young Infants: Is It Safe to Watch and Wait? Report of a SIOPEN Observational Study Results.

Background: To assess whether expectant observation of infants ≤ 90 days old with small suprarenal masses (sSRMs) could avoid unnecessary surgery without impacting outcome. Methods: Infants ≤ 90 days with a ≤ 5 cm mass, without midline extension or lymph node or distant spread were registered (ClinicalTrials.org:NCT01728155). Once staging was completed, they were followed with ultrasound, MRI and urinary catecholamines. Surgical resection was only planned if there was a ≥40% mass volume increase or for a mass persisting after 48 weeks of the planned observation. Results: Over a 5-year period, 128 infants were registered. No infant had detectable MYCN amplification in the peripheral blood. Surgery was performed in 39 (30.5%) patients, in 18 during and in 21 after the planned 48-week observation, and 74% were confirmed to be neuroblastomas. Non-life-threatening surgical complications occurred in two cases. The 3-year overall survival and event-free survival were 100% and 87.1%, respectively. The 16 events observed were volume increase (N = 11) and progression to neuroblastoma stage MS (N = 5). Patients with solid masses or MIBG-positive masses had lower EFS. Conclusions: Expectant observation for infants with sSRMs with clinical follow-up and timely imaging (including MRI scan) is safe and effective, allowing surgery to be avoided in the majority of them.

Genomic Analysis Made It Possible to Identify Gene-Driver Alterations Covering the Time Window between Diagnosis of Neuroblastoma 4S and the Progression to Stage 4.

Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1, MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients.

New Insights into Iron Deficiency Anemia in Children: A Practical Review.

Iron deficiency anemia (IDA) is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39 and 48.1% in developing countries). Although IDA has been recognized for a long time, there are still uncovered issues and room for improving the management of this condition. New frontiers regarding its diagnosis and therapeutic options emerge every day; recently, innovative formulations of iron have been launched, both for oral and parenteral administration, with the aim of offering treatment schedules with higher efficacy and lower toxicity. As a matter of fact, glycinate and liposomal preparations, while maintaining a satisfying efficacy profile, have significantly fewer side effects, in comparison to the traditional elemental iron salts; parenteral iron, usually considered a second-choice therapy reserved to selected cases, may evolve further, as a consequence of the production of molecules with an interesting clinical profile such as ferrocarboxymaltose, which is already available for adolescents aged >14 years. The present article reports the clinically relevant latest insights regarding IDA in children and offers a practical guide to help pediatricians, particularly to choose the most appropriate prevention and therapy strategies.

Pleuro-pulmonary ultrasound in the diagnosis and follow-up of lung infections in children with cancer: a pilot study.

PURPOSE: Febrile neutropenia and lung infections are common and potential fatal complications of pediatric cancer patients during chemotherapy. Lung ultrasound (LUS) has a good accuracy in the diagnosis of pneumonia in childhood, but there is no data concerning its use in the diagnosis and follow-up of pulmonary infection in children with cancer. The goal of this pilot study is to verify the feasibility of lung ultrasonography for the diagnosis and follow up of pneumonia in children and adolescents with cancer. MATERIAL AND METHODS: This is a prospective observational case-control monocentric study conducted in the Pediatric Hematology and Oncology Department of University Hospital of Catania in patients aged < 18 years with cancer. Attending Physician used ultrasonography to detect pneumonia in cancer children with fever. As control group, cancer patients with no infection suspicion were also tested. LUS results were compared to chest X-ray (CXR) and/or chest CT scan, when these imaging techniques were performed, according to clinical indication. RESULTS: Thirty-eight patients were studied. All underwent LUS, 16 underwent CXR, 3 chest CT. Statistical analysis showed LUS specificity of 93% (95% CI 84-100%), and sensitivity of 100%; CXR, instead, showed a specificity of 83% (95% CI 62-100%) and a sensitivity of 50% (95% CI 1-99%). CONCLUSION: This study shows for the first time that LUS allows physicians to diagnose pneumonia in children and young adults with cancer, with high specificity and sensitivity.

Bilateral adrenal primary tumor in Stage 4S neuroblastoma: The Italian experience and review of the literature.

Bilateral adrenal neuroblastoma (NB) is rare and is mainly stage 4S. Its incidence, presenting features, management, and outcome have not been fully defined yet. We searched the Italian NB Registry (RINB) for stage 4S NB infants with bilateral adrenal primary tumor to compare them with stage 4S NB with unilateral tumor. Between 1979 and 2016, the RINB enrolled 3731 NB patients aged 0-18 years including 317 infants (8.5%) diagnosed with stage 4S NB. Eleven/317 (3.5%) had a bilateral adrenal primary tumor (Group 1) and 190/317 (59.9%) had a unilateral tumor (Group 2). Group 1 infants were significantly younger (51 vs. 89 days) but were comparable with Group 2 for any other presenting features. In the absence of specific protocols, upfront treatment was based on symptoms, size of adrenal tumors, and biology, and consisted of observation in 5 cases, radiotherapy in one, chemotherapy in 2, and surgery in 3. Five/11 developed progression and 2 of them, both with MYCN amplification, died. The 5-year EFS rates of Group 1 and 2 were 54.5% vs. 73.3% (P=.14) and 5-year OSs were 81.8% and 89.4%, respectively (P=.44). Our data support the hypothesis that 4S NB infants with bilateral adrenal tumors can have favorable outcome with personalized therapeutic approach. The three patients with MYCN amplified tumor benefited from upfront aggressive chemotherapy, in accordance with current protocols. Because of the rarity of this intriguing form of neuroblastoma, collaborative prospective studies are warranted, especially in view of gaining a better insight on its biological and genetic features.

Influence of Body Mass Index, Cancer Type and Treatment on Long-Term Metabolic and Liver Outcomes in Childhood Cancer Survivors.

In the last decade, the survival of subjects affected by cancer in childhood has significantly improved. The increased lifespan of childhood cancer survivors (CCS) led to a greater risk for long-term, therapy-related morbidity. To identify the clinical predictors of metabolic adverse outcomes in CCS (average off-therapy period: 12 years), we recruited 126 survivors of different childhood cancers (86.5% hematological cancers) who received at least anticancer chemotherapy, consecutively approached during their annual oncohematological outpatient visit. At examination, anthropometric measures and cancer-related history were collected. Moreover, a fasting venous sample was carried out for measuring fasting plasma glucose and insulin, glycated hemoglobin, lipid panel, and transaminases. We calculated the indexes of insulin resistance (HOMA-IR, McAuley, and QUICKI) and secretion (HOMA-ß), liver steatosis (Hepatic Steatosis Index) and fibrosis (FIB-4 and NAFLD fibrosis score), and visceral fat dysfunction (Visceral Adiposity Index). More than one-third of the subjects (37.3%) did not have normal weight, with 11.1% of them affected by obesity. At recruitment, obese subjects were at significantly higher risk for impaired fasting glucose, metabolic syndrome, visceral adipose dysfunction, and liver steatosis/fibrosis. Subjects who received bone marrow transplantation were prone to insulin resistance, while survivors of lymphoma presented a visceral adipose dysfunction These results suggest a carefully metabolic monitoring of CCS, particularly in subgroups at higher risk, to early detect these conditions, promptly begin therapeutic interventions, and mitigate the dysmetabolic-related health burden.

Preserved Long-Term Lung Function in Young Adult Survivors of Common Childhood and Adolescence Malignancies.

Purpose: We aimed to evaluate long-term lung function and respiratory outcomes in young adults who survived common pediatric malignancies, treated in a single center. Methods: We enrolled young adults who had been treated during their childhood or adolescence for hematological or solid cancer at our Pediatric Oncology Unit, and performed pulmonary function tests (PFT) and clinical evaluation. PFT included spirometry and Diffusing Capacity of Lung for Carbon Monoxide (DLCO). Results: We included 121 survivors, mean age 23 years at follow-up, median 15 years from diagnosis. The most common diagnoses were hematological malignancies, mainly acute lymphoblastic leukemia, whereas 31% of the patients were treated for nonhematological cancer, mainly neuroblastoma. Treatments consisted of chemotherapy alone or in combination with radiotherapy and/or hematopoietic stem cell transplantation. Most of the patients denied respiratory symptoms throughout the years. In the whole group only eight patients (6%) had abnormal PFT, consisting mainly in a restrictive pattern and reduced DLCO. PFT abnormalities were of mild degree in most of the cases. Overall, the mean values of forced vital capacity, forced expiratory volume in 1 second, and DLCO were normal, but lower in females, in those who received radiotherapy and in those treated for lymphoma. Conclusion: In a group of young adults, surviving the most common childhood malignancies, we found a preserved lung function after a median follow-up of 15 years. The constantly increasing survival in childhood cancer is now associated with a trend toward an improvement in long-term respiratory outcomes.

WT1 and Cyclin D1 Immunohistochemistry: A Useful Adjunct for Diagnosis of Pediatric Small Round Blue Cell Tumors on Small Biopsies.

Pediatric small round blue cell tumors (SRBCTs) are a heterogeneous group of neoplasms with overlapping morphological appearance. Accordingly, their diagnosis is one of the most difficult in the field of surgical pathology. The most common tumors include rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma, lymphoblastic lymphoma and Wilms' tumor (the blastemal component). Over time their diagnosis has become more difficult due to the increasing use of small biopsies. However, the advent of immunohistochemistry has improved the quality of diagnosis in most cases by the application of an adequate panel of immunomarkers. Recently, WT1 and Cyclin D1 have been shown to be useful in the differential diagnosis of SRBCTs on surgically-resected specimens, showing a diffuse cytoplasmic positivity of the former in all RMSs and a diffuse nuclear staining of the latter in both EWS and NB. The aim of the present study was to investigate the expression of WT1 and Cyclin D1 on small biopsies from a series of 105 pediatric SRBCTs to evaluate their diagnostic utility. Both immunomarkers were differentially expressed, with a diffuse and strong cytoplasmic staining for WT1 limited to all cases of RMS, and a diffuse nuclear staining for cyclin D1 restricted to all cases of EWS and NB. Notably, the expression of WT1 and cyclin D1 was also retained in those cases in which the conventional tumor markers (myogenin, desmin and MyoD1 for RMS; CD99 for EWS; NB84 for NB) were focally expressed or more rarely absent. The present study shows that WT1 and Cyclin D1 are helpful immunomarkers exploitable in the differential diagnosis of pediatric SRBCTs on small biopsies, suggesting their applicability in routine practice.

Risk of Benign and Malignant Thyroid Disorders in Subjects Treated for Paediatric/Adolescent Neoplasia: Role of Morphological and Functional Screening.

BACKGROUND: Patients treated for paediatric/adolescent (P/A) neoplasia have a high incidence of both benign and malignant thyroid diseases. Given the high incidence of sequelae, literature data show a clinical benefit of morpho-functional thyroid screening in paediatric/adolescent cancer survivors and a careful lifetime follow-up. PATIENTS AND METHODS: The incidence of thyroid alterations was evaluated in a consecutive series of 343 patients treated with chemotherapy (CHE) and radiotherapy (RTE) or only with CHE for P/A tumours between 1976 and 2018 (mean age at time of primary paediatric malignancy 7.8 ± 4.7 years). All patients underwent thyroidal morpho-functional evaluation between 2000 and 2019. RESULTS: 178 patients (51.9%) were treated only with CHE and 165 (48.1%) with CHE+RTE. A functional and/or structural thyroid disease was diagnosed in 147 (42.5%; 24.2% in CHE and 62.4% in CHE+RTE group; p = 0.0001). Of note, 71 (20.7%) patients with no evidence of disease at first evaluation developed a thyroid alteration during the follow-up. Primitive hypothyroidism was diagnosed in 54 patients (15.7%; 11.2% in CHE vs. 20.6% in CHE+RTE group; p = 0.01) and hyperthyroidism in 4. Sixty-three patients developed thyroid nodules (18.4%; 4.0% in CHE and 14.1% in CHE+RTE group; p < 0.001); thyroid cancer was diagnosed in 30 patients (8.7%; 4.5% in CHE and 12.4% in CHE + RTE group; p = 0.007). CONCLUSIONS: In patients treated with CHE+RTE, the prevalence of hypothyroidism and nodular pathology, both malignant and benign, were significantly greater than in patients treated with CHE. However, also in the CHE group, the frequency of thyroid disease is not negligible and the pathogenetic mechanisms remain to be clarified. Our data suggest the clinical benefit of morpho-functional thyroid screening in P/A cancer survivors.

Spinal cord compression as tumor onset: an unusual case report of Hodgkin lymphoma in a teenager.

BACKGROUND: Spinal cord compression (SCC) is an uncommon, severe complication of Hodgkin lymphoma (HL), occurring in 0.2% of cases at the onset and in 6% during disease progression. We present a teenager with SCC with clinical onset of HL; her pre-existing neurological abnormalities covered the presence of an epidural mass, which could have misled us. CASE PRESENTATION: A 13-year-old girl presented with a three-month history of lower back pain and degrading ability to walk. She suffered from a chronic gait disorder due to her preterm birth. A magnetic resonance imaging of the spine revealed an epidural mass causing collapse of twelfth thoracic vertebra and thus compression and displacement of the spinal cord. Histological examination with immunohistochemical analysis of the epidural mass demonstrated a classic-type Hodgkin lymphoma. Early pathology-specific treatment allowed to avoid urgent surgery, achieve survival and restore of neurological function. CONCLUSIONS: Children and adolescents with back pain and neurological abnormalities should be prioritized to avoid diagnostic delay resulting in potential loss of neurological function. SCC requires a prompt radiological assessment and an expert multidisciplinary management.

Psychopathological outcomes and defence mechanisms in clinically healed adults with a paediatric cancer history: an exploratory study.

BACKGROUND: The incidence of paediatric cancers has increased in recent years; however, with advances in the treatment of paediatric cancer, almost 80% of children and adolescents who receive a diagnosis of cancer become long-term survivors. Given the high stress levels associated with cancer, it becomes important to ascertain the risk and likelihood of psychiatric disorders in adult paediatric cancer survivors. AIMS: This study aims to investigate the relationship between defence styles and predisposition to psychiatric diseases in adults with a history of paediatric cancer. METHODS: We performed an explorative study on a sample of 66 clinically healed adults with a history of paediatric cancer (survivors) during follow-up visits at the University Hospital 'Policlinico G Rodolico' of Catania (Italy) and 98 healthy controls among medicine students. We administered the Defence Mechanism Inventory (DMI) to assess defence styles. The Symptom Checklist-90-Revised (SCL-90-R) and the Davidson Trauma Scale (DTS) were administered to assess psychopathological indices. We conducted comprehensive statistical analysis based on correlation analysis and mediation analysis to investigate the relationship between defence styles and psychopathological outcomes in survivors compared with controls. RESULTS: The survivors obtained statistically significant lower values in TAO, PRO and TAS defence styles and a higher value in REV. Both groups showed non-pathlogical mean scores in DTS and SCL-90-R (with an exception of the obsessive-compulsive subscale), with lower mean values among survivors. The results of mediation analysis showed that TAS had mediation effects on interpersonal sensitivity, anxiety, PSDI, GSI and avoidance, while TAO had mediation effects on DTS total score and intrusivity. Thus, for these psychopathological indices, the effect of the oncological pathology was indirect and mediated by TAO or TAS. Our analysis exlcluded mediation effects between the remaining variables and defence styles. CONCLUSION: Integrating data from mediation and correlation analysis, we found how the decreasing of TAS utilization in survivors as the consequence of cancer history, has decreased interpersonal sensitivity, anxiety and GSI score in these subjects compared with controls. Similary, the decrease of TAO utilization played a role in lower values of DTS total score and intrusivity subscale. Unexpectedly, our analysis excluded relationships between cancer history, other defence styles and psycopathological scores as we initially assumed.

Desmoplastic Small Round Cell Tumor with "Pure" Spindle Cell Morphology and Novel EWS-WT1 Fusion Transcript: Expanding the Morphological and Molecular Spectrum of This Rare Entity.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare pediatric soft tissue neoplasm composed of small round tumor cells with prominent stromal desmoplasia, polyphenotypic differentiation and EWSR1-WT1 gene fusion. We, herein, present a unique case of DSRCT, exhibiting a pure spindle cell morphology, absence of desmoplastic stroma and showing a novel EWS-WT1 fusion transcript. METHODS: A 12-year-old boy presented multiple intra-abdominal, confluent and mass-forming nodules that affected the entire abdominal and pelvic cavities. RESULTS: Histologically, the nodules were composed of spindle cells with scant cytoplasm and oval nuclei arranged into short, intersecting fascicles and set in a scant, non-desmoplastic, stroma. Immunohistochemically, neoplastic cells were stained with vimentin, desmin, WT-1 (C-terminus antibodies) and EMA. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed the presence of an unusual chimeric transcript, composed of an in-frame junction of exon 9 of EWS to exon 7 of WT1, confirming the histological diagnosis of DSRCT. CONCLUSIONS: The present case contributes to widen the morphological spectrum of this entity; notably, the additional presence of a novel chimeric fusion transcript contributes to making the present case even more unique. Whether the detection of the above-mentioned fusion transcripts could explain the unusual morphology of the tumor remains to be established.

Malignant sacrococcygeal germ cell tumors in childhood: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience.

PURPOSE: To evaluate clinical features at diagnosis, prognostic factors, and outcomes of malignant sacrococcygeal germ cell tumors (SC-GCTs) in patients enrolled in the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) TCG 2004 protocol. PATIENTS AND METHODS: A prospective analysis was conducted on all consecutive patients diagnosed with malignant SC-GCTs between January 2004 and May 2017. Patients with stage I underwent surgery and subsequent surveillance, the others received pediatric cisplatinum-etoposide-bleomycin (pPEB) regimen and eventual deferred surgery. RESULTS: Of 45 patients, 35 were females. Age at diagnosis ranged from 1 day to 3.6 years (median 1.6 years); 26 were stage IV. Of 38 patients who underwent surgery, pathology revealed yolk sac tumor (YST) in 27 and teratoma + YST/embryonal carcinoma in 11, while seven patients were diagnosed based on imaging and elevated levels of alpha-fetoprotein (AFP). Of six patients approached with surgery, only one relapsed and was rescued with first-line chemotherapy. Overall, 38 out of 45 achieved complete remission, three a partial remission, and four were resistant. Ten out of 41 patients who entered remission later relapsed and nine were rescued with a second-line treatment. We observed a global failure percentage of 31% and a 5-year overall survival (OS) and event-free survival (EFS) of 95% and 69%, respectively. CONCLUSIONS: Chemotherapyis generally effective in malignant SC-GCTs, even though almost one-third of our patients experienced events salvageable with second-line treatment. Most of the relapses occurred within 1 year from diagnosis. A close follow up with serial AFP level monitoring should be done for at least 2 years after diagnosis.

Self- and Parent-Reported Psychological Symptoms in Young Cancer Survivors and Control Peers: Results from a Clinical Center.

Pediatric cancer survivors are at increased risk for psychological distress. We sought to understand the severity and symptoms' co-occurrence among pediatric survivors compared to controls by rating both self- and parent-reported symptomatology. Forty survivors (22 males; mean age at study time: 12.9 years) participated in the study. Most survivors (85%) had a diagnosis of acute lymphoblastic leukemia. Seventy-nine healthy controls with the same age and gender distribution as the patients were included. A standardized assessment of psychological functioning was conducted by self- and parent-reported symptoms evaluations. The self-reported anxious symptom severity was significantly higher in survivors. A significantly higher proportion of survivors compared to controls had clinically significant anxiety, depression, and combined anxiety symptoms (i.e., social anxiety, separation anxiety, or physical symptoms). In both study groups, the self-reported emotional and somatic symptoms were significantly associated. The multi-informant assessments of the psychological symptoms revealed distinct associations between the child- and parent-reported symptoms in the survivors' group: the survivors' self-reports of depressive symptoms, somatic symptoms, and functional impairment were significantly correlated with the parent reports of child behavioral concerns, somatic complaints, and functional impairment, respectively. Conclusion: Self-reported symptoms showed similar comorbidity profiles in survivors and control peers. The multi-informant assessments detected differences in the association of self- and parent-reported symptoms between the survivor and control groups. The present study showed that multi-informant assessment is critical to understanding symptom profiles and to informing intervention with particular regard to parental participation and support.