Viralization due to Leydig cell tumor diagnosis by magnetic resonance imaging. Case management report

A 3-year-old boy who presented with signs of virilization had a Leydig cell tumor of the left testis that could not be detected by physical examination or by high resolution ultrasonography. His very small tumor was demonstrated by magnetic resonance imaging. The implications of adding this sensitive method of imaging to the evaluation of prepubertal virilization of presumed testicular etiology are discussed.     

Undifferentiated (Embryonal) Liver Sarcoma of Childhood: Evidence of Leiomyoblastic Differentiation

This report describes the clinical, histopathologic, and ultrastructural features of a tumor of the liver arising in an 11-month-old infant and displaying the morphology of undifferentiated (embryonal) sarcoma. The floss presentation and clinical manifestations showed some overlap with features often considered distinctive of embryonal rhabdomyosarcoma primary of bile ducts. However, electron microscopic study disclosed only fibroblastic and leiomyoblastic differentiation in biopsies of recurrent tumor, close to 2 years after the original diagnosis. Theoretical implications of this finding are discussed.     

Undifferentiated (embryonal) liver sarcoma of childhood: evidence of leiomyoblastic differentiation

This report describes the clinical, histopathologic, and ultrastructural features of a tumor of the liver arising in an 11-month-old infant and displaying the morphology of undifferentiated (embryonal) sarcoma. The gross presentation and clinical manifestations showed some overlap with features often considered distinctive of embryonal rhabdomyosarcoma primary of bile ducts. However, electron microscopic study disclosed only fibroblastic and leiomyoblastic differentiation in biopsies of recurrent tumor, close to 2 years after the original diagnosis. Theoretical implications of this finding are discussed.     

Association of prolonged fever and hypernatremia: rare presentation of hypothalamic/third ventricle tumor in a toddler

The authors describe a 2-year-old boy with a clinical presentation of prolonged fever of unknown origin and severe hypernatremia. This rare association was the result of a hypothalamic/third ventricle tumor. The lesion was removed and was found to be a low-grade neuronal tumor. After surgery, the child did generally well, but hypothalamic thermoregulatory and osmoregulatory functions were not restored. These presenting symptoms, their pathophysiology, and the implications for pediatric practice are discussed.     

细胞因子在淋巴瘤患者发热时病因鉴别诊断中的作用

发热是淋巴瘤患者常见的临床症状,淋巴瘤患者发热的病因大致有肿瘤伴感染所致的发热、肿瘤本身引起的发热以及化疗药物和生物制剂所致的药物热.常用的感染标志物超敏C反应蛋白(high-sensitivity C-reactive protein,hsCRP)、血清降钙素原(procalcitonin,PCT)等对区分感染性发热、肿瘤性发热及药物热是无效的,但淋巴瘤患者的上述三种发热病因均与细胞因子关系密切.细胞因子可能有助于淋巴瘤患者发热时病因的鉴别诊断,这既可改善患者预后,也避免了淋巴瘤患儿的抗生素滥用.该文综述了细胞因子在淋巴瘤患者上述发热病因中的鉴别诊断作用.     

How I approach hereditary cancer predisposition in a child with cancer

Approximately 10% of all children with cancer are affected by a monogenic cancer predisposition syndrome. This has important implications for both the child and her/his family. The assessment of hereditary cancer predisposition is a challenging task for clinicians and genetic counselors in daily routine. It includes consideration of tumor genetics, specific features of the patient, and the medical/family history. To keep up with the pace of this rapidly evolving and increasingly complex field of genetic susceptibility, we suggest a systematic approach for the evaluation of the child with cancer and her/his family by an interdisciplinary team specialized in hereditary cancer predisposition.     

Patients with primary brain tumors as organ donors: case report and review of the literature

Malignancy is considered a contra-indication to organ donation, with a few possible exceptions. We present the case of a child with fatal intracranial hemorrhage from a primary brain tumor (PBT) whose organs were denied for transplant after recovery. We review the literature of organ donors with PBTs in the context of the current organ shortage and discuss the implications for the practicing oncologist. Transmission of donor brain tumor to organ recipients has been documented but the incidence appears to be very low. Risk factors for tumor transmission include underlying donor tumor histology, history of craniotomy and/or shunt placement, use of systemic chemotherapy and radiation therapy, and duration of disease prior to donation. Ongoing data collection by national registries will provide more information on the potential risk to organ recipients. It may be appropriate to expand the donor pool to include donors with PBTs in certain situations. The transplantation team ultimately decides upon the use of organs from specific donors. Many families will appreciate the opportunity to donate specific tissues even if solid organ transplantation is prohibited.     

A rare case of retinocytoma occurring in a 12-year-old child

A 12-year-old girl with a translucent, partially calcified retinal mass in the posterior pole surrounded by a rim of pigment epithelial changes and chorioretinal atrophy was diagnosed as having retinocytoma. The patient received a single treatment of transpupillary thermotherapy at the slit lamp to prevent malignant transformation. The dimensions of the lesion and the visual acuity remained unchanged at 3.5 years of follow-up with no further treatment. Retinocytoma is a benign retinal tumor that carries the same genetic implications as retinoblastoma. Regular follow-up is necessary because the tumor can demonstrate malignant transformation.     

Cardiorespiratory fitness in survivors of pediatric posterior fossa tumor

Advances in medical therapies have greatly improved survivorship rates in children diagnosed with brain tumor; as a result, morbidities associated with survivorship have become increasingly important to identify and address. In general, pediatric posterior fossa tumor survivors tend to be less physically active than peers. This may be related to late effects of diagnosis and treatment, including cardiovascular, endocrine, psychological, and neurocognitive difficulties. Exercise has been shown to be effective in improving physical functioning, mood, and even cognitive functioning. Consequently, the benefits of physical exercise need to be explored and incorporated into the daily lives of pediatric posterior fossa tumor survivors. The primary aim of the present study was to establish the feasibility and safety of cardiorespiratory fitness testing in pediatric posterior fossa tumor survivors who had received cranial radiation therapy. In addition, comparing our cohort with previously published data, we found that pediatric posterior fossa tumor survivors tended to be less fit than children with pulmonary disease and healthy controls and approximately as fit as children with chronic heart disease and survivors of other types of childhood cancer. The importance of cardiorespiratory fitness in pediatric posterior fossa tumor survivors is discussed along with implications for future directions.     

Growth factors and oncogenes in brain tumors: the model of glioblastoma and medulloblastoma]

Glioblastomas and medulloblastomas are models for studying the implication of growth factors and oncogenes in tumor development. Amplification and/or hyperexpression of oncogenes result in products that may mimic growth factors and/or their receptors; cells may demonstrate autocrine and/or paracrine activity. Prognostic implications of such findings are suggested.     

Left ventricular rhabdomyoma causing subaortic stenosis—the two-dimensional echocardiographic appearance

Summary We report the preoperative and postoperative clinical findings, M-mode and two-dimensional echocardiograms, and the cardiac catheterization findings in a newborn with left ventricular rhabdomyoma causing severe subaortic stenosis. The tumor was diagnosed by echocardiography at 3 hours of age. The clinical implications of the case are discussed.     

Study design and cohort characteristics of the Childhood Cancer Survivor Study: a multi-institutional collaborative project

BACKGROUND: Increased attention has been directed toward the long-term health outcomes of survivors of childhood cancer. To facilitate such research, a multi-institutional consortium established the Childhood Cancer Survivor Study (CCSS), a large, diverse, and well-characterized cohort of 5-year survivors of childhood and adolescent cancer. PROCEDURE: Eligibility for the CCSS cohort included a selected group of cancer diagnoses prior to age 21 years between 1970-1986 and survival for at least 5 years. RESULTS: A total of 20,276 eligible subjects were identified from the 25 contributing institutions, of whom 15% are considered lost to follow-up. Currently, 14,054 subjects (69.3% of the eligible cohort) have participated by completing a 24-page baseline questionnaire. The distribution of first diagnoses includes leukemia (33%), lymphoma (21%), neuroblastoma (7%), CNS tumor (13%), bone tumor (8%), kidney tumor (9%), and soft-tissue sarcoma (9%). Abstraction of medical records for chemotherapy, radiation therapy, and surgical procedures has been successfully completed for 98% of study participants. Overall, 78% received radiotherapy and 73% chemotherapy. CONCLUSION: The CCSS represents the largest and most extensively characterized cohort of childhood and adolescent cancer survivors in North America. It serves as a resource for addressing important issues such as risk of second malignancies, endocrine and reproductive outcome, cardiopulmonary complications, and psychosocial implications, among this unique and ever-growing population.     

Congenital defects in the interferon-gamma/interleukin-12 pathway

PURPOSE OF REVIEW: The aim of this review is to highlight the most recent and relevant advances in the interferon-gamma/interleukin-12 pathway, a pivotal player of the immune system, and their repercussions on basic and clinical aspects of science. RECENT FINDINGS: Newly described mutations are helping us to dissect the interferon-gamma/interleukin-12 pathway and its role in genetic infectious susceptibility and autoimmunity, and to reevaluate the pathophysiologic mechanisms involved in dominant and recessively inherited mutations. SUMMARY: The interferon-gamma/interleukin-12 pathway plays a central role in immune control of both environmental and autochthonous challenges, as reflected in human mutations and animal models. Besides being crucial for mycobacterial control, the interferon-gamma/interleukin-12 pathway is also involved in the pathogenesis of autoimmune disease, as well as tumor development and control. Genotype-phenotype correlations have been established for certain mutants in this pathway, some of which have therapeutic implications.     

Myoclonic encephalopathy of infants or "dancing eyes syndrome". Report of 7 cases with long-term follow-up and review of the literature (cases with and without neuroblastoma).

We describe 7 children with myoclonic encephalopathy of infants (MEI). MEI is a clinical entity characterized by an acute or subacute onset of polymyoclonia, cerebellar ataxia and opsoclonus ("dancing eyes"). It occurs either spontaneously, following an infectiuos illness or in association with an occult neuroblastoma. It is likely that immunological factors play a role in the pathogenesis. Steroid therapy resulted in rapid dramatic improvement of the neurological symptoms in 4 cases. However, this initial response did not correlate with the eventual outcome. We reviewed the literature to compare 45 reported cases of MEI associated with a neuroblastoma with 48 children without such a tumor to identify possible differences in clinical presentation, response to steroid medication and long-term prognosis of the neurological syndrome. In this respect we found no differences. Impairment of motor, verbal or intellectual performance were reported in at least half the cases. Although an immediate and marked response to steroids occurs in many cases of both groups, it remains unclear whether the long-term outcome is favourably influenced by this medication. The two-year-survival rate (90%) in the neuroblastoma group and the percentage of mediastinal localisation of the tumor (49%) are much higher compared with neuroblastomas without MEI. The reasons for these remarkable differences are not known. Diagnostic, therapeutic and prognostic implications justify the separation of MEI from the more common and benign syndrome known as acute cerebellar ataxia of childhood.     

Radiation-induced meningioma following prophylactic radiotherapy for acute lymphoblastic leukemia in childhood

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Although it was considered to be a poor prognostic disease, modern treatment protocols (aggressive chemotherapy and prophylactic cranial irradiation) have resulted in dramatically improved survival rates. In a group of low-risk ALL patients, the 5-year survival rate is estimated to be 85%. However, ALL patients who undergo this treatment are at risk of developing secondary neoplasms related to treatment, which has become an increasingly recognized problem. CASE DESCRIPTION: A 3-year-old boy with ALL was successfully treated with chemotherapy (vincristine, prednisolone, mercaptopurine and methotrexate) and prophylactic cranial irradiation (total 18 Gy). At the age of 23, he was admitted to our hospital for weakness in the right leg. Computed tomography and magnetic resonance imaging revealed a parasagittal tumor of the left frontoparietal lobe with perifocal edema. The tumor was completely removed surgically and pathohistologically diagnosed as atypical meningioma. CONCLUSION: Long-term survivors who received radiotherapy for ALL in childhood are at risk for late complications, including radiation-induced meningioma. Therefore, careful follow-up neurological examinations, for example magnetic resonance imaging, are indicated in these patients. In addition, late complications should be taken into account during the initial planning of prophylactic radiotheraphy dosage, which has implications for informed consent of the patient.     

The role of neoadjuvant chemotherapy in children with malignant solid tumors

Pediatric surgeons play a critical role in diagnosing, staging, and treating malignant solid tumors in children. Over the years, the surgical management of the primary tumor site has evolved from an aggressive en-bloc resection at diagnosis to a more tailored surgical approach, often affecting definitive local control after the delivery of neoadjuvant therapy, as currently directed by many solid tumor protocols. In fact, inappropriate upfront resection can lead to unnecessary short- and long-term morbidity, an incomplete resection, and may be associated with a delay in the initiation of the systemic chemotherapy that is critical to the treatment of gross or occult metastatic disease. Therefore, it is important for the pediatric surgeon, as a member of the multidisciplinary team involved in the care of these children, to understand the indications for and implications of neoadjuvant therapy in the treatment of pediatric solid tumors. Here we review the current management of childhood solid tumors focusing on the role of neoadjuvant therapy.     

Critical observations on neuroblastoma treatment with 131-I-metaiodobenzylguanidine at diagnosis

Results of treatment with 131-I-Metaiodobenzylguanidine (131-I-MIBG) in patients with resistant neuroblastoma appear encouraging if one considers that most of the patients had far advanced, intensively pre-treated disease. To further explore the potential role of this new drug in untreated patients, we treated 3 children with stage III neuroblastoma. All three of our cases received 131-I-MIBG at relatively low dose with the complete disappearance of the tumor mass in case 1, whereas in cases 2 and 3 CT scan showed a significant reduction of the tumor mass and, interestingly enough, no evidence of 131-I-MIBG uptake of a tracer dose in the remaining tumor. Particularly, in case 2, the persistence and subsequent progression of part of the tumor mass without 131-I-MIBG uptake after a therapeutic dose of 131-I-MIBG, which apparently destroyed the 131-I-MIBG-positive cell population, clearly suggest heterogeneity at diagnosis, with a dual neuroblastoma cell population, one with 131-I-MIBG uptake and the other without. Besides the biological implications of the 131-I-MIBG uptake heterogeneity in neuroblastoma at diagnosis, our findings suggest that in stage III neuroblastoma patients even a relatively small dose of 131-I-MIBG administered at diagnosis is sufficient to destroy either the primary tumor completely (case 1) or the part of the tumor (case 2 and 3) which shows 131-I-MIBG uptake, without any significant hematologic toxicity. Furthermore, a single course of 131-I-MIBG at the dosage employed does not appear to jeopardize the subsequent use of chemotherapy. In conclusion, if our data are confirmed by further investigation, 131-I-MIBG may be included as a front line drug shortly followed by chemotherapy in future treatment strategies of advanced neuroblastoma without or with minimal bone marrow infiltration. © 1993 Wiley-Liss, Inc.     

VISUAL PATHWAY TUMOR: A Heterogeneous Tumor With a Variable Clinical Course

The aim of the study was to delineate the clinical characteristics of visual pathway tumor in children without neurofibromatosis-I. The authors reviewed the charts of all patients meeting these criteria ( n = 12) who were followed in their center over a 13-year period. In 8 patients the disease was relentlessly progressive, and imaging showed a chiasmatic/hypothalamic, exophytic globular lesion. The remainder had a benign course with long periods of tumor stability; one showed some spontaneous visual improvement. The lesions of the latter subgroup were multilobular, with elongated posterior extension into the optic tract. This differentiation, according to the imaging findings, may have significant therapeutic implications. In the first type, every effort should be made to arrest the disease and decrease the size of the lesion, whereas in the second, despite decreased visual ability, careful observation in the appropriate approach. There are as yet no known biological markers to better delineate these two types of tumor behavior.