The New Reality is VirtualWilliam L. Carroll, MD*Perlmutter Cancer Center, NYU-Langone Medical Center, New York, New York*Correspondence to: William L. Carroll, MD Division of Pediatric Hematology-Oncology, Departments of Pediatrics and Pathology, Perlmutter Cancer Center, NYU-Langone Medical Center, 560 East First Avenue, Smilow Room 1211, New York, NY, 10016E-mail: William.email@example.comThe COVID-19 pandemic led to a precipitous and severe disruption to healthcare delivery and consumption worldwide. Ongoing analyses (and debate) about the effectiveness of early response measures will continue, but there is no doubt the pandemic brought about dramatic changes to health care, some of which are likely to last.The health care industry is built on a model of in-person visits between patients and providers, which is reinforced by economic incentives. However, tremendous pressure was put on health care systems to pivot quickly from in-person visits given the explosive spread of COVID-19. Non-essential in-person visits and elective procedures were reduced, or paused, allowing hospitals to marshal capacity for a surge in COVID-19 cases and to mitigate risk of infection to patients and staff. Patients deferred care, in many cases with negative results1. Outpatient in-person volume plummeted over 40%2.In any crisis, opportunities emerge and telehealth visits surged providing a safe alternative to in-person visits3. Telehealth or virtual visits are not novel and has been in place since the mid 1990’s especially for rural care but regulation and reimbursement limited its application4. With changes in payer reimbursement, telehealth visits increased dramatically. Early in the pandemic up to a third of office visits were through virtual care. This trend was most pronounced in primary care and mental health/psychiatry but whether it can be applied safely to patients with complex conditions requiring therapy with medications associated with a narrow therapeutic index like cancer is less certain.In this issue of Pediatric Blood and Cancer Rabinowicz et al, raise the question of how essential are in-person visits during maintenance therapy for B acute lymphoblastic leukemia (ALL), the most common childhood cancer5. The authors conducted a retrospective study to determine if an in-person visit was essential to detect an abnormal finding on physical examination especially if it resulted in a change in medical management. They excluded patients during the first three months of maintenance when more frequent laboratory evaluations are needed to titrate medication dosages, when children required intrathecal or intravenous therapy, or when other specialists saw patients. All others could be considered candidates for virtual care delivery. Seventy-five children with 240 routine visits were analyzed. Fourteen were associated with a new abnormal finding and in only six cases was a direct physical examination deemed required for diagnosis. Only three such visits resulted in a change in medical management. Based on these results, the authors argue, justifiably, that there is a large potential for virtual visits during maintenance treatment.The results of this study are not surprising especially as most patients, including the fourteen with new findings on exam in this report, will have symptoms (not analyzed in the study) alerting parents and providers to new medical conditions warranting in-person visits. Most ALL treatment protocols mandate physical examination with routine laboratory monitoring on a monthly basis and it is hard to justify more frequent intervals in the absence of follow up medication adjustments or specific problems. There might a subset of families with particular hardships related to travel where the in-person interval can be extended further. COG protocols now use every 12 week vincristine/decadron pulses with intrathecal methotrexate administration. Home phlebotomy services have been piloted to obtain laboratory blood draws and perform port flushes6. Virtual visits can be used to ascertain any side effects, adjust medications, and emphasize compliance. Another positive aspect of the pandemic is the widespread adaption of at home viral testing and there is no doubt that COVID-19 has changed the future of in-home medical diagnostics.The authors provided a thoughtful, balanced analyses and discussion of the pros, including decreasing the burden of care (e.g. school absences, time off work for parents, and transportation costs) and cons of virtual visits. Two important considerations are warranted when deciding on frequency of virtual vs. in-person visits. First, a “digital divide” is well described where limited access to high-speed internet services, lower socioeconomic status and limited English proficiency are barriers to access. Second, medical monitoring is only one part of a broader strategy in pediatric cancer care to decrease the physical, neuropsychological, educational and financial burden of cancer on children and their families. Thus, children and their families may routinely interact with physicians, nurses, social workers, physical therapists, child life therapists, teachers and psychologists as part of a personalized care model during clinic visits. Such multidisciplinary services may be difficult to replicate through virtual care delivery.It is also time to consider other aspects of digital technology that can enhance the health of our patients and their families7. Mobile health is especially attractive as the overwhelming majority of adults and adolescents have access to a smartphone8. Applications such as MyChart (EPIC) allows patients and parents to view their electronic record in real time and interact with providers. Multiple studies have shown that customized, interactive apps can also be used to augment education about disease and management, manage side effects such as nausea and vomiting, and promote medication adherence9,10. It is time to accelerate the implementation of these tools in every day practice.The article by Rabinowicz and colleagues should motivate us to consider implementing and expanding adaptive strategies developed in response to the COVID-19 pandemic to improve patient care for children and their families with cancer. Virtual visits can never completely replace in-person visits where emotional bonds and trust between providers and patients are required to promote optimal outcomes. However after such relationships are cemented early in treatment virtual visits can reduce the burden of therapy without sacrificing quality.1. Quarello P, Ferrari A, Mascarin M, et al. Diagnostic Delay in Adolescents with Cancer During COVID-19 Pandemic: A New Price for Our Patients to Pay. J Adolesc Young Adult Oncol. 2021.2. Dupraz J, Le Pogam MA, Peytremann-Bridevaux I. Early impact of the COVID-19 pandemic on in-person outpatient care utilisation: a rapid review. BMJ Open. 2022;12(3):e056086.3. Uscher-Pines L, McCullough C, Dworsky MS, et al. Use of Telehealth Across Pediatric Subspecialties Before and During the COVID-19 Pandemic.JAMA Netw Open. 2022;5(3):e224759.4. Werner RM, Glied SA. Covid-Induced Changes in Health Care Delivery - Can They Last? N Engl J Med. 2021;385(10):868-870.5. Rabinowicz R, Maguire B, Hitzler J, Punnett A. How Essential are In-Person Clinic Visits During Maintenance Treatment of Children with Acute Lymphoblastic Leukemia? Pediatric Blood & Cancer. 2022.6. Sisler I, Cohen D, Skinner LA, Aiken C, Laver J. Feasibility of a Pilot Home Phlebotomy Program for Pediatric Hematology/Oncology Patients During the COVID-19 Pandemic. J Pediatr Hematol Oncol.2022;44(1):e185-e187.7. Keesara S, Jonas A, Schulman K. Covid-19 and Health Care’s Digital Revolution. N Engl J Med. 2020;382(23):e82.8. Nievas Soriano BJ, Uribe-Toril J, Ruiz-Real JL, Parron-Carreno T. Pediatric apps: what are they for? A scoping review. Eur J Pediatr. 2022;181(4):1321-1327.9. Heneghan MB, Hussain T, Barrera L, et al. Access to Technology and Preferences for an mHealth Intervention to Promote Medication Adherence in Pediatric Acute Lymphoblastic Leukemia: Approach Leveraging Behavior Change Techniques. J Med Internet Res. 2021;23(2):e24893.10. Semerci R, Akgun Kostak M, Taskin C. The effect of using an interactive mobile application for the management of chemotherapy-induced nausea and vomiting in children: Randomized controlled study. Eur J Oncol Nurs. 2022;58:102121.
A Novel MECOM Variant Associated with Congenital Amegakaryocytic Thrombocytopenia and Radioulnar Synostosis Hanan Al-Abboh1, Akmal Zahra1 and Adekunle Adekile1,2Pediatric Hematology Unit, Mubarak Hospital1 and Department of Pediatrics, Faculty of Medicine, Kuwait University2, Kuwait Address Correspondence to: Professor Adekunle Adekile Department of Pediatrics Faculty of Medicine Kuwait University PO Box 24923 Safat 13110 Kuwait Email: firstname.lastname@example.org Tel: +96525319486To the EditorCongenital radioulnar synostosis (RUS) is a rare developmental anomaly of proximal fusion of the radius and ulna, resulting in limited pronation and supination of the forearm. It may accompany other abnormalities in the skeleton, kidney, heart and aneuploidy syndromes1,2. A subset of patients with RUS present with bone marrow failure (BMF) syndromes, characterized by amegakaryocytic thrombocytopenia (RUSAT), progressing to myelodysplasia and pancytopenia2,3. The hematological manifestations are quite variable, with some presenting with severe BMF in childhood, while others are mild and may not present until adulthood.Heterozygous germline variants in the homeobox A11 (HOXA11) gene were the first to be associated with RUS and designated RUSAT14, but lately, several families have been described with variants in the MDS1 and EVI1 complex (MECOM) locus, and referred to as RUSAT22,5,6. Many of these variants appear de novo , while others follow an autosomal dominant inheritance. We, hereby, report the case of a Kuwaiti patient who presented with congenital amegakaryocytic thrombocytopenia (CAMT) in the neonatal period and later noticed to have RUS. Whole exome sequencing revealed a novel MECOM variant.A.A. is a male Kuwaiti, the first child of consanguineous parents and was first seen at the age of 36 days, following antenatal ultrasound diagnosis of bilateral hydronephrosis and right renal cyst. He was a product of induced vaginal delivery with a birth weight of 2.3 kg. After delivery, he was kept under observation in the neonatal intensive care unit. His CBC showed isolated thrombocytopenia (Plt 34 x109/L). He received several platelet transfusions, as well as IVIG twice. Postnatal abdominal ultrasound showed multicystic right kidney, in addition to bilateral hydronephrosis. The mother had no history of thrombocytopenia during pregnancy and there was no other pertinent family history.Physical examination at presentation showed 2 café-au-lait spots, one on the back, measuring 1x2 cm and another over the left leg, that was less than 0.6 cm. There were no obvious dysmorphic features and other systems were unremarkable. CBC showed WBC 11.2 x109/L Hb 10.4 g/dL, MCV 83fl, Plt 49 x109/L, ANC 1.8 x109/L. Renal function tests were normal. Blood film showed no abnormal cells; there was true thrombocytopenia with giant forms. Antiplatelet antibody was negative. Abdominal ultrasound at age 1 month showed complete replacement of the right kidney by cystic changes with left moderate hydronephrosis. Skeletal survey was reportedly normal.Bone marrow biopsy showed normal distribution of granulocytic and erythroid precursors, with severe suppression of megakaryocytosis, consistent with a bone marrow failure syndrome. Chromosomal breakage study was normal. The patient was diagnosed with right undescended testis, as well as right inguinal hernia that were operated at age 1 year and 10 months. At the age 2 and a half years, A.A. was noticed to have limited bilateral arm movement supination and pronation. The mother volunteered that she has a similar defect. X-rays confirmed that the child had bilateral radioulnar synostosis. Whole exome sequencing showed that the patient is heterozygous for a previously-unreported MECOM gene, c.2282A>G mutation. Unfortunately, the parents have not been screened for these mutations.The patient has been under follow up for 4 years, his platelet count has been stable, ranging between 40-50 x109/L, with no bleeding tendency. In spite of his limited arm rotation, he currently functions normally in his daily activities, however, his hand writing skills and ability to engage in sports are yet to be observed since he is still pre-school age. Platelet transfusion is reserved only for severe bleeding, which he has not had. Bone marrow transplant may be considered in future if his bone marrow failure worsens and/or his marrow shows dysplastic changes.Dokal et al3 were the first to report an association between RUS and late-onset BMF, while Thompson et al described its association with CAMT and linked it to the c.872delA ,p.Asn291Thrfs3 variant of the HOXA11gene4,7. More recently, several germline mutations in the MECOM locus have been reported and appear to be the more common cause of RUSAT. Indeed, no other cases of HOXA11 mutations linked to RUSAT have been described since the initial report. Niihori et al8 reported the first 3 heterozygous MECOMmutations in 3 sporadic patients. These variants and those subsequently reported by Walne et al2 are in a highly conserved cluster within 10 amino acids (aa750-760) and impact on either the highly conserved Cys2His2 zinc finger motif (zinc finger 8, aa733-755) or the adjacent linker motif (aa756-760). It has been shown that removal of the 8th zinc finger causes granulopoiesis arrest while mutations and deletions in other parts of the complex, outside the 8th and 9th fingers, are associated with hematological disorders without RUS9.MECOM codes for a zinc finger transcription factor with important roles in normal development and oncogenesis and is involved in the regulation of embryonic development and hematopoietic stem-cell renewal. Hence the phenotype in individuals with these mutations is very variable ranging from BMF to different skeletal, cardiac, renal malformations, B cell deficiency and sensorineural deafness.Our patient showed a previously unreported variant in the region of the 8th zinc finger of the MECOM locus. This c.2282A>G missense variant results in the tyrosine to cysteine substitution at codon 761 (p.Tyr761Cys). The amino acid is in the Zinc finger, C2H2 and Zinc finger, C2H2-like protein domains and is highly evolutionarily conserved. Unfortunately, the parents were not screened for the mutation, however, the mother shows RUS, with normal blood counts. This is consistent with the marked variability in the clinical phenotype. The father is also physically and hematologically normal.Apart from thrombocytopenia, our patient also had renal abnormalities – hydronephrosis and multicystic kidney disease. The natural history of his condition is that he may develop pancytopenia and/or myelodysplasia in the future. He is under close follow up and will be considered for bone marrow transplantation if his condition worsens. In the meantime, he remains hypomegakaryocytic with a platelet count at 30 – 50 x 109/l while other blood cellular elements are normal. His renal function and hearing are being monitored, but still remain normal.AcknowledgementsWe thank the patient’s family for allowing us to report this case. The whole exome sequencing was done at the Laboratory of Genetics and Genomics, Cincinnati Children’s Hospital, Cincinnati, Ohio.References1. Rizzo R, Pavone V, Corsello G, Sorge G, Neri G, Opitz JM. Autosomal dominant and sporadic radio-ulnar synostosis. Am J Med Genet.1997;68(2):127-134.2. Walne A, Tummala H, Ellison A, et al. Expanding the phenotypic and genetic spectrum of radioulnar synostosis associated hematological disease. Haematologica. 2018;103(7):e284-e287.3. Dokal I, Ganly P, Riebero I, et al. Late onset bone marrow failure associated with proximal fusion of radius and ulna: a new syndrome.Br J Haematol. 1989;71(2):277-280.4. Thompson AA, Nguyen LT. Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation. Nat Genet. 2000;26(4):397-398.5. Germeshausen M, Ancliff P, Estrada J, et al. MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia. Blood Adv. 2018;2(6):586-596.6. Ripperger T, Hofmann W, Koch JC, et al. MDS1 and EVI1 complex locus (MECOM): a novel candidate gene for hereditary hematological malignancies. Haematologica. 2018;103(2):e55-e58.7. Thompson AA, Woodruff K, Feig SA, Nguyen LT, Schanen NC. Congenital thrombocytopenia and radio-ulnar synostosis: a new familial syndrome.Br J Haematol. 2001;113(4):866-870.8. Niihori T, Ouchi-Uchiyama M, Sasahara Y, et al. Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia. Am J Hum Genet.2015;97(6):848-854.9. Nielsen M, Vermont CL, Aten E, et al. Deletion of the 3q26 region including the EVI1 and MDS1 genes in a neonate with congenital thrombocytopenia and subsequent aplastic anaemia. J Med Genet.2012;49(9):598-600.
Purpose: Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard-of-care has not been established due to a paucity of data. Methods: A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. Results: Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9 years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n=13; 31.7%), followed by posterior fossa (n=7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, one from pneumonia and one from Moyamoya following radiation-therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types – 62% germinomas, 79% for NGGCTs, and 53% for teratomas. Conclusion: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.
Comment on: Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement.Matthew J. Murray1,2, Nigel J. Hall3, Sara Stoneham4, Anthony Penn5, Mark Brougham6, James C. Nicholson1,7; on behalf of the Children’s Cancer and Leukaemia Group (CCLG) Germ Cell Tumour (GCT) Special Interest Group (SIG).1 Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK2 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK3 University Surgery Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK4 Department of Paediatrics and Child Health, University College Hospital London NHS Foundation Trust, London, UK5 Department of Paediatric Oncology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL, UK6 Department of Paediatric Oncology, Royal Hospital for Children & Young People, 50 Little France Crescent, Edinburgh bio Quarter, Edinburgh, EH16 4TJ, UK7 Department of Paediatrics, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UKConflict of interest statement : the authors declare no conflicts of interest.We read with interest the article from Braungart and colleagues, discussing management of young females with benign ovarian tumors . This is important and timely, and we agree with the need for clarity in management of this under-investigated group. As the authors note, published evidence to support decisions is limited, so in certain areas, guidance may have to rely on expert opinion. The authors emphasize the importance of multidisciplinary team (MDT) discussion to optimise management and risk-stratification . They highlight the importance and safety of ovarian-sparing-surgery in benign tumors, to preserve fertility and avoid long-term effects including premature ovarian failure .However, important aspects of their methodology are unclear. The denominator (number of experts approached to be involved) and response rate is not stated. The standard thresholds for accepting Delphi statements is >70% votes in support from >60% of experts in each voting round , as used in Delphi studies undertaken by the authors here [3,4]. Furthermore, there is no indication of level of support for statement(s) not reaching the 70% threshold. Moreover, they list specialties involved without defining numbers in each group, preventing assessment of the work’s objectivity and relative representation. Frequent criticisms of Delphi method work are poor questionnaire/statement design, compounded by inadequate definition/ selection of experts . For example, ‘the inclusion of other clinicians… may be appropriate to provide an alternative clinical view, particularly when the study is expected to have an impact beyond a particular specialist field’ . Of particular note, the study states that a ‘…. Delphi panel was instigated that included… pediatric oncologists representing CCLG Germ Cell Tumour Group’ . Unfortunately, there was no pediatric oncologist involvement from the group in formulating the statements for discussion. Subsequently, only one was invited to participate in the Delphi itself, once the statements had been finalized. Furthermore, there was no patient/parent representation in the Delphi process, crucial to involve for a benign disease, with issues regarding surgical approach, fertility, and the burden of proposed ultrasound follow-up.The surgical guidance is useful; however, a size cut-off for minimally invasive surgery is specified, without supportive evidence . Another incongruity is for tumor marker follow-up (section 2.3, bullet 7) if they were elevated preoperatively; by definition this group should have had normal markers at diagnosis (section 2.1, first paragraph) . In the follow-up section (2.3), bullet-points 3-5 are most contentious as no evidence is presented for dictating time-interval to scan, and a recent systematic review looking at this indication, which concluded, based on available evidence, that ‘routine surveillance… should certainly be considered’ and suggested annual ultrasound , was overlooked. In addition, no reference is provided here to existing guidelines . The recommended two-year interval between ultrasounds  is therefore neither evidence-based nor considers the patient/parent opinion. Furthermore, there is no justification for gynecologic fertility referral following ovarian-sparing-surgery where subsequent ultrasound shows normal ovarian reserve bilaterally. Consequently, terms relating to specific aspects that ‘should’ include/be undertaken/performed are inappropriate. Suggesting that ‘a reasonable strategy that could be considered might be as follows…’ would be a better approach.In summary, attempts to improve the management of young females with benign ovarian tumors are laudable. Some of the surgical recommendations made should help to streamline care. However, a representative group of key stakeholders were not included in the Delphi method and most of the follow-up recommendations cannot be justified based on use of a limited group of experts with limited supporting evidence. What is required is a wider collaborative approach, including GCT, surgical, gynecologic, radiology, and importantly patient groups, to answer these questions more robustly, preferably with international collaboration. This will also ensure appropriate clinician engagement, minimise inconsistencies in management and optimise outcomes for this patient group.
The International Soft-Tissue Sarcoma Database Consortium (INSTRuCT) consists of a collaboration between the Children’s Oncology Group (COG) Soft Tissue Sarcoma Committee, the European pediatric Soft-Tissue Sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). As part of the larger initiative of INSTRuCT to provide consensus expert opinions for clinical treatment of pediatric soft tissue sarcoma, we sought to provide updated, evidenced-based consensus guidelines for local treatment of parameningeal rhabdomyosarcoma using both existing literature as well as recommendations from the relevant cooperative group clinical trials. Overall, parameningeal rhabdomyosarcoma represents a distinctly challenging disease to treat given its location near many critical structures in the head and neck, frequently advanced local presentation, and predilection for local failure. Definitive chemoradiation remains the standard treatment approach for parameningeal rhabdomyosarcoma, with surgery often limited to biopsy or salvage therapy for recurrent disease. In this consensus paper, we specifically discuss consensus guidelines and evidence for definitive local management with radiotherapy, with a focus on imaging for radiotherapy planning, dose and timing of radiation, approach for nodal irradiation, various radiation techniques including proton therapy, and the limited role of surgical resection.
GLUTEUS AS A RARE LOCALIZATION OF EXTRAGONADAL TERATOMAAuthorship: Leardini Davide 1, Cerasi Sara1, Cantarini Maria Elena 1, Facchini Elena 1, Prete Arcangelo 1, Masetti Riccardo 11 Pediatric Oncology and Hematology Unit ”Lalla Seràgnoli”, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyCorrespondence: Sara Cerasi; address: via G. Massarenti 11, 40138, Bologna (BO), Italy; phone: +39 051 2144665; e-mail:email@example.comWord Count for Main Text: 547 wordsAttached to this manuscript there is 1 figureKeywords: extragonadal teratoma, gluteal mass, immature teratomaRunning title: Rare non-midline teratomaTo the Editor,Teratomas represent the most common germ cell tumors in children1. They can be gonadal, more common in adolescents, or extragonadal, primarily in neonates and young children. Teratomas develop from totipotent primordial cells and may originate anywhere along the midline. Common sites for extragonadal teratomas are the sacrococcygeal region, which accounts for 35-60% of all teratomas, the mediastinum, the retroperitoneum, the head and neck and the central nervous system2–4. Other localizations are rare, especially non-midline ones that are very often lateralized expansions of midline teratomas, such as those arising from sacrococcygeal region.We here describe the case of a newborn girl presenting with a gluteal mass, that revealed to be a primary extragonadal teratoma. At birth she presented with a hard-elastic, mobile and painless mass localized within the right gluteus (Fig.1), that had not been noted on prenatal ultrasound. At two days of life, an echography was performed, revealing a subcutaneous irregularly hypoechoic mass with fluid areas inside and small vessels, with aspecific characteristics. The dimension of the mass was 24x15 mm and rapidly increased in size, reaching 40x25mm, and in the number of fluid areas (Fig. 1). Alfafetoprotein serum concentration resulted 4586 ng/mL (refence value at the 2 week-1 month interval at which she was tested 316-6310 ng/mL) and hCG was 0,8 UI/L (normal value <5 UI/L)5. After performing an MRI that excluded other lesions, the mass was removed and a biopsy was performed, revealing an immature teratoma, grade 3 according to Norris’s classification. Since extragonadal teratomas out of the midline are very rare, she has been followed up thoroughly for 3 years with regular periodic blood tests and radiological assessments, but no other primary lesions or recurrencies were found.Teratomas can be malignant (12-14%) or benign, further divided into mature (50-60%) and immature (18-34%). Immature teratomas contain fetal tissue, most often neuroectodermal, the amount of which is scored according to a grading system introduced by Norris. Grade 3 is that with most neuroectodermal tissue, and have an increased incidence of local recurrence and malignant degeneration3,4,6. Complete and prompt surgical resection is the gold standard for definitive therapy in benign teratomas, both mature and immature4,6.Teratomas develop along the midline because they originate from the incomplete differentiation of totipotent primordial cells that arise in the yolk sac and migrate along the mesentery to the gonadal ridge during the 4th-5th week of embryologic development3,4. Indeed, most of the gluteal teratomas reported in literature are lateralized sacrococcygeal teratomas with a connection to the coccyx, since sacrococcygeal teratomas are thought to be derived from totipotent cells of the Hensen’s node (primitive knot), an area at the cranial end of the primitive streak7,6.Other authors reported rare sites for lateralized teratoma development such as kidney, liver and temporozygomatic region8,9. Rare lateralized extragonadal localizations should not mislead the clinical suspicion of teratomas, and a primary localization should always be excluded. Taking also the patient’s age into account, it can sometimes be considered to perform a PET scan. To the best of our knowledge, there is just one case in literature of a gluteal teratoma not in connection with the coccyx, as in our patient, thus confirming the possibility of this very rare localization10. The biological mechanism for germ-cell migration in such anatomical regions is still to be elucidated.ACKNOWLEDGEMENTS: None.CONFLICT OF INTERESTThe authors declare that there is no conflict of interest.ETHICS STATEMENTWritten informed consent has been obtained from the patient to publish this paper.
Objectives To investigate the extent to which observer variability of CT lung nodule assessment may affect clinical treatment stratification in Wilms Tumor (WT) patients, according to the recent SIOP-RTSG UMBRELLA protocol. Methods I: CT thoraces of children with WT submitted for central review, were used to estimate size distribution of lung metastases. II: Scans were selected for blinded review by five radiologists to determine intra and inter-observer variability. They assessed identical scans on two occasions six months apart. III: Monte Carlo simulation (MCMC) was used to predict the clinical impact of observer variation when applying the UMBRELLA protocol size criteria. Results Lung nodules were found in 84 out of 360 (23%) children with WT. For 21 identified lung nodules, inter-observer limits of agreement (LOA) for the five readers were ±2.4mm and ±1.4mm (AP diameter), ±1.9mm and ±1.8mm (TS diameter) and ±2.0mm and ±2.4mm (LS diameter) at assessments 1 and 2. Intra-observer LOA across the three dimensions were ±1.5mm, ±2.2mm, ±3.5mm, ±3.1mm and ± 2.6mm (readers 1-5). MCMC demonstrated that 17% of the patients with a ‘true’ nodule size of 3mm will be scored as <3 mm, and 21% of the patients with a ‘true’ nodule size of <3mm will be scored as being 3 mm. Conclusion A significant intra-inter observer-variation was found when measuring lung nodules on CT for patients with WT. This may have significant implications on treatment stratification, and thereby outcome, when applying a threshold of 3 mm for a lung nodule to dictate metastatic status.
Lynch syndrome (LS) is the most common hereditary colon cancer syndrome caused by germline mutations in mismatch repair (MMR) genes. In this series, we outline 3 pediatric patients who presented with vague symptoms due to colorectal cancer who were eventually diagnosed with Lynch syndrome with multiple gene mutations. The diagnosis of colorectal cancer in pediatrics warrants timely recognition, inclusion of Lynch syndrome in the differential diagnosis, multi-gene testing, and genetic counseling for the patient and family.
Pain in children living with and beyond cancer is understudied and undertreated. Pain science education (PSE) is a conceptual change strategy facilitating patients’ understanding of the biopsychosocial aspects of pain. Preliminary studies on the adaptation of PSE interventions to adults with and beyond cancer provide a foundation for pediatric research. PSE could help childhood cancer survivors experiencing persistent pain and pain-related worry after active treatment. PSE may also help children receiving cancer treatment, providing them with a foundation of adaptive pain beliefs and cognitions, and preparing them for procedural and treatment-related pain. We direct this paper towards pediatric oncology clinicians, policy makers and researchers working with children living with and beyond cancer. We aim to; (1) identify challenges in adapting PSE for children living with and beyond cancer, (2) offer possible solutions, and (3) propose research questions to guide the implementation of PSE for children living with and beyond cancer.
Comment on: Burden of central nervous system complications in sickle cell disease: A systematic review and meta-analysis R. Grant Steen, PhD103 Van Doren PlaceChapel Hill, NC 27517G_Steen_MediCC@yahoo.comDear Editor;I read with interest a recent paper in Pediatric Blood & Cancer(1), about cognitive impairment in children with sickle cell disease (SCD). I’m always grateful to have my work cited, especially since our paper is almost 20 years old (2).However, it seems that Lee et al . have gone to great lengths to mischaracterize our work. They write (pg. 5) that, “SCI [silent cerebral infarct] and absence of SCI/CVA [cerebrovascular accident] were verified by review of brain MRIs in all studies except Ghafuri et al . and Steen et al . In these studies, absence of SCI/CVA was defined as no mention of cerebral infarcts in the subject’s medical records.” Also on pg. 5, they write that, “An alternative analysis was conducted excluding studies with insufficient definition of overt stroke and/or SCI based on clinical opinion (Ghafuriet al . and Steen et al .)”. I cannot speak for Ghafuriet al , but we did a careful review of MRI findings for every single patient in our study, as is necessary for a paper in theAmerican Journal of Neuroradiology . This should be pellucidly clear because the title of our paper is, “Cognitive Impairment in Children with Hemoglobin SS Sickle Cell Disease: Relationship to MR Imaging Findings and Hematocrit ”. All our SCD patients were evaluated by at least two neuroradiologists, and patients thought to be abnormal were evaluated by a third neuroradiologist blinded as to previous findings (2). One wonders what other errors may be present in Leeet al (1).Fortunately, this mischaracterization of our work did not lead to incorrect conclusions (1). A comparison of Table 1 to Supplementary Table 6, in which our paper and Ghafuri et al were deleted from analysis, shows that none of the major findings were changed much by deleting these papers (1). I agree with most conclusions in Lee et al .; in fact, I would go further. In uncited work from St. Jude Children’s Research Hospital, we found that children with SCD can suffer cognitive impairment even in the absence of MRI evidence of brain injury (3). We tested a hypothesis that children with SCD who are completely normal by MRI can still be cognitively impaired, as predicted by a model of diffuse brain injury. A total of 54 patients with hemoglobin SS (average age 10.9 years ± 2.9 years SD) were examined with the Wechsler Intelligence Scale for Children-III (WISC-III) and were randomly matched by age, race, and gender to healthy children from the Wechsler normative database. Patients were also imaged at 1.5 Tesla with standard imaging sequences. Among 30 patients judged normal by MRI, there were substantial deficits in Wechsler Full-Scale IQ, Verbal IQ, and Performance IQ (all P < 0.01), when compared to African-American controls. The patient Wechsler Full-Scale IQ was 12.9 points lower than that of matched controls and decreased as a function of age (P = 0.014). These findings strongly suggest that there is diffuse brain injury in SCD patients, perhaps associated with chronic hypoxia (3).