Rare tumors in childhood: Pathological aspects. Experience of the Kiel pediatric tumor registry

A wide variety of rare tumors can occur in childhood and adolescence. Tumors can be rare in any age group; common tumors of adults can appear in childhood and adolescence, and many rare tumors and tumor-like lesions show a predilection for younger age groups. Comparatively frequent tumors can present with rare histologic features or can occur in rare atypical locations, and, finally, seemingly common but, in fact, rare tumors have to be distinguished from truly common but rarely recognized tumors. Thus, the spectrum of rare tumors is broad, reflecting the fluent reality of life. © 1993 Wiley-Liss, Inc.     

Brainstem tumors: where are we today?

Brainstem tumors comprise 10-20% of all pediatric central nervous system tumors. The management of these tumors has evolved dramatically in the past century. Once considered uniformly fatal, it is now known that brainstem tumors have distinguishing characteristics and do not behave identically. The focality and location of the lesion is determined from the clinical history, presentation, and associated imaging. Based on these findings, it is possible to predict the behavior of the tumor and choose an appropriate intervention. Focal lesions have a good prognosis and are treated operatively while diffuse lesions have a poor prognosis and are managed medically. This article reviews the current classification of brainstem tumors, current management options and future directions for the treatment of these rare tumors.     

Management of Childhood Brain Tumors: Consensus Report by the Pediatric Hematology Oncology (PHO) Chapter of Indian Academy of Pediatrics (IAP)

Brain tumors are the second most common childhood tumors and remain the leading cause of cancer related deaths in children. Appropriate diagnosis and management of these tumors are essential to improve survival. There are no clinical practical guidelines available for the management of brain tumors in India. This document is a consensus report prepared after a National Consultation on Pediatric Brain Tumors held in Delhi on 06 Nov 2008. The meeting was attended by eminent experts from all over the country, in the fields of Neurosurgery, Radiation Oncology, Pediatric Oncology, Neuropathology, Diagnostic Imaging, Pediatric Endocrinology and Allied Health Professionals. This article highlights that physicians looking after children with brain tumors should work as part of a multidisciplinary team to improve the survival, quality of life, neuro-cognitive outcomes and standards of care for children with brain tumors. Recommendations for when to suspect, diagnostic workup, initial management, long-term follow up and specific management of individual tumors are outlined.     

Massive congenital intracranial immature teratoma of the lateral ventricle with retro-orbital extension: a case report and review of the literature

Germ cell tumors comprise 0.4-3.1% of all intracranial tumors, and teratoma constitutes 9-30% of them. Congenital intracranial tumors are very rare and only account for 0.5-1.5% of all childhood brain tumors. The most common type of these tumors present at birth is teratomas, which represent 0.5% of all intracranial tumors. Most teratomas are midline tumors located predominantly in the sellar and pineal regions. In this study, we report a neonatal intracranial immature teratoma at the lateral ventricle because of its rare location. A 5-day-old female neonate presented with a history of irritability and left eye protrusion since birth. A head computed tomographic (CT) scan and magnetic resonance imaging (MRI) disclosed a large tumor filling the left lateral ventricle and extending into the ipsilateral retro-orbital space. With left frontotemporoparietal craniotomy, a large grayish-white lobulated vascular mass was encountered, and total removal of tumor was performed. Histological examination revealed the diagnosis of immature teratoma. The prognosis of congenital intracranial immature teratoma is usually poor because the lesions are extensive when they are identified. Prenatal ultrasonography is necessary for the prenatal diagnosis. Fetal MRI should be made for the evaluation of intracranial tumor. If the tumor is detected before the 24th week of gestation, termination of the pregnancy should be considered.     

Treatment Refusal and Abandonment in Children with Acute Lymphoblastic Leukemia

The importance of a uniform coding system for cancer research, tumor registry, and exchange of information is recognized. However, tumors arising in children differ from those in adults, resulting in lack of precision when one coding system is used for both. Because the topographic code of the International Classification of Disease for Oncology for adult tumors does not lend itself well to pediatric tumors, the International Society of Paediatric Oncology (SIOP) developed a four-digit topographic coding system particularly adapted to childhood tumors. The four digits correspond to anatomic site, general and specific localization, and tissue of origin. An SIOP pilot study demonstrated the usefulness of this code.     

三岁以下低龄儿童原发性脑肿瘤临床回顾与分析

目的 回顾性分析5年间我院3岁以下低龄儿童原发性脑肿瘤的临床、病理特点以及预后情况.方法 自2006年1月至2010年12月间,我院共收治87例3岁以下原发性脑肿瘤患儿,通过手术治疗的同时获得其组织病理学报告,根据WHO2007年新分类,分析该年龄组患儿的临床症状、组织学类型、病理分级、治疗方案的特点以及影响预后的相关因素.结果 该年龄组患儿以男性居多,脑肿瘤幕上多于幕下,并以中线部位多见.神经上皮肿瘤为最多见病理类型,按发病率排序的肿瘤类型依次为:低级别星形细胞瘤(20.7％)、髓母细胞瘤(13.8％)、室管膜肿瘤(12.6％)以及脉络丛乳头状瘤(12.6％).患儿的临床表现以头围增大(48.3％)、呕吐(36.8％)、肌力下降(19.5％)以及抽搐(16.1％)为主.预后与肿瘤位置、肿瘤病理、年龄以及手术切除程度有关.结论 3岁以下年龄组患儿的预后较大龄儿童差,手术治疗仍为低龄患儿的首选治疗方案,围手术期处理以及术后辅助治疗的加强为今后工作研究的重点.     

P53 Protein Expression in Hepatoblastoma: An Immunohistochemical Investigation

Mutations of the p53 tumor suppressor gene with immunohistochemically detectable expression of p53 protein have been described in many different malignant tumors. In this study, 12 hepatoblastomas of various subtypes were investigated immunohistochemically with a monoclonal antibody for the expression of p53 protein. Immunoreactivity for p53 protein was found in both small cell tumors investigated and in embryonal areas in two out of eight tumors, but not fetal (eight tumors) or mesenchymal (four tumors) areas. The findings show that immunohistochemically detectable expression of p53 protein, which generally indicates mutation of the gene, may also be present in hepatoblastoma. The finding of p53 protein immunoreactivity in both of the small cell tumors but none of the fetal areas is consistent with a proposal in the literature concerning the histogenesis and differentiation of the various subtypes—that fetal hepatoblastoma is the most well-differentiated and small cell hepatoblastoma the least well-differentiated subtype.     

Malignant adrenal tumors

Adrenal tumors, apart from neuroblastoma, are relatively rare in infancy and childhood. Most adrenal lesions are benign, and both benign and malignant tumors may be hormonally active thus, making accurate preoperative diagnosis difficult. The two main malignant tumors are adrenocortical carcinoma and pheochromocytoma. In both tumors, it may be difficult to determine benign from malignant and the biologic behavior and degree of invasion may portend a more malignant course. Surgical excision is the primary therapy for both tumors, including excision of metastatic and recurrent tumor. An open procedure should be considered for invasive adrenocortical carcinoma and in pheochromocytomas in which preoperative imaging demonstrates metastatic nodal disease. A laparoscopic approach is preferred for lesions in which preoperative imaging demonstrates a localized lesion. Chemotherapy, although without proven efficacy, is utilized in some children with metastatic or unresectable disease.     

Pediatric germ cell tumors

Pediatric germ cell tumors represent a diverse group of tumors that present from in utero through adolescence at many nongonadal locations, from the neck to the sacrococcygeal region. Surgical resection remains the central element of management, and accurate surgical staging is essential to properly ascertain the correct risk-based treatment. The management for all benign tumors (mature and immature teratomas) and select completely resectable malignant tumors is surgery alone. Modern-day chemotherapy is extremely effective in infants and children with unresectable and metastatic disease and these children have a very high survival rate. The use of neoadjuvant chemotherapy allows vital organ preservation and there is no role for resection of vital structures at the time of initial presentation.     

EFFECTS OF FOOD SUPPLEMENTATION AND EDUCATION ON FOLATE STORES

Neuroblastoma (NB) is the most common extracranial malignant solid tumors of childhood, and the majority of these high-risk tumors is resistant to nearly all the treatments and has a significantly worse outcome. The mammalian target of rapamycin (mTOR) plays a critical role in oncogenesis and cancer progression of many tumors. This review will describe the function of mTOR, its genetic regulation in pediatric neuroblastoma, and its value as a target for inhibition by anticancer agents for patients with NB.     

Topography of childhood tumors: pediatric coding system

The importance of a uniform coding system for cancer research, tumor registry, and exchange of information is recognized. However, tumors arising in children differ from those in adults, resulting in lack of precision when one coding system is used for both. Because the topographic code of the International Classification of Disease for Oncology for adult tumors does not lend itself well to pediatric tumors, the International Society of Paediatric Oncology (SIOP) developed a four-digit topographic coding system particularly adapted to childhood tumors. The four digits correspond to anatomic site, general and specific localization, and tissue of origin. An SIOP pilot study demonstrated the usefulness of this code.     

Follow-up and risk of tumors in overgrowth syndromes

A striking feature of the overgrowth syndromes (OGS) is the risk of cancer. In some OGS (Beckwith-Wiedemann, Perlman, Simpson-Golabi-Behmel syndromes and hemihypertrophy) tumors appeared mostly in the abdomen (more than 94% of tumors), are usually diagnosed before 10 years, and most of them are embryonal. Conversely, in other OGS, such as Sotos syndrome, the most frequent type is lympho-hematological tumors, about two-thirds are extra-abdominal and some of these tumors may appear after the second decade of life. Based on a previous literature review, a specific schedule protocol for tumor screening was suggested for many OGS. In this article we briefly review some aspects of the current knowledge of OGS and tumors, emphasizing the follow-up of these disorders.     

Cytogenetics in pediatric low-grade astrocytomas

BACKGROUND: Cytogenetic analysis in certain tumors is a vital part of classification and assignment of prognosis. Few studies have examined the value of cytogenetic analysis in pediatric brain tumors. This is especially true of low-grade astrocytomas (LGA) of childhood. This study examines the correlation between cytogenetic abnormalities and survival in children with low-grade astrocytomas. The literature on adults with LGA suggest better survival for those whose tumors have normal cytogenetics compared to those with abnormal. We hypothesized this would also be true of children with low-grade astrocytomas. PROCEDURE: A retrospective study was performed of children presenting between 1980 and 1998 to The Children's Hospital, Denver, who had LGA and on whose tumors informative cytogenetics had obtained. RESULTS: One hundred and forty-nine children were diagnosed with histologically proven LGA. Twenty-nine had successful cytogenetic analysis. One or more chromosomal abnormalities were observed in eight tumors while normal karyotypes were observed in 21 tumors. Actuarial progression-free survival at 5 years was 87.5% for the eight children with abnormal cytogenetics and 43% for those with normal (P=0.56). Overall survival at 5 years was 83% for those with abnormal cytogenetics and 78% for those with normal (P=0.8). The differences in progression-free survival and overall survival between these two groups were not significant. Those children with WHO Grade I tumors had significantly superior progression-free and overall survival than those with Grade II tumors. CONCLUSIONS: It appears unlikely that, for children with LGA, those with normal cytogenetics have a better prognosis than those with abnormal. Histologic grade is a better predictor of outcome than cytogenetics.     

Childhood brain tumors

Primary malignant tumors of the central nervous system (CNS) account for about 16% of all childhood malignancies. These tumors are the second most common type of childhood cancer and the most frequent of the solid tumors. The small increase in incidence noted over the past two decades most likely represents advancements in diagnostic technologies rather than true changes in disease frequency, though this is controversial. CNS tumors are diverse, representing many histological types and arising in a variety of anatomic sites. The most common malignant tumors include astrocytomas (52%), medulloblastomas/primitive neuroectodermal tumors (PNETs) (21%), gliomas (19%), and ependymomas (9%). The current 5-year survival rate for all pediatric CNS tumors is 67%, but rates differ considerably among tumor types. Treatment modalities also differ according to histological type. Currently, about 25% of patients are treated with surgery alone, 40% undergo surgery plus radiation, and 30% are treated with surgery, radiation, and chemotherapy. Survivors of childhood brain tumors are at substantial risk for increased morbidity and late mortality. Five-year survivors of brain tumors are 13 times more likely to die than healthy age- and sex-matched peers. Disease recurrence remains the single most common cause of late deaths (70%). Neurological, neurocognitive, and endocrine disturbances are the most prevalent disabilities observed among long-term survivors of pediatric brain tumors.     

The role of high‐dose chemotherapy and stem cell rescue in the treatment of malignant brain tumors: A reappraisal

Abstract: The outcome for children with malignant brain tumors has improved modestly in recent years. Notable is the improved 5‐yr disease‐free survival for those children with 'standard‐risk' medulloblastoma and other primitive neuro‐ectodermal tumors (PNET) (i.e. tumors without neuraxis dissemination at presentation). For other children with newly diagnosed malignant brain tumors, especially in the absence of radical surgical resection, the outcome remains poor despite surgery, irradiation and conventional chemotherapy. Patients whose tumors recur despite initial therapy continue to experience a dismal outlook with these conventional strategies of treatment. In an attempt to improve the outlook for such brain tumor patients with poor prognoses, strategies utilizing high‐dose (potentially myeloablative) chemotherapy with autologous stem cell rescue have been developed. These studies, conducted initially in patients with recurrent tumors, were then extended to patients with newly diagnosed malignant gliomas and brain‐stem tumors, as well as to young children with various malignant brain tumors at diagnosis in an attempt to avoid irradiation to the brain. The results of several of these studies are summarized, updating information reviewed in an earlier summary in 1996, demonstrating durable disease‐free survival for a proportion of patients with recurrent malignant gliomas and medulloblastomas/PNET, as well as encouraging data in some of those patients with newly diagnosed brain tumors.     

Management of ovarian and testicular sex cord-stromal tumors in children and adolescents

Pediatric ovarian and testicular sex cord-stromal tumors are distinct from germ cell neoplasms and may present with palpable mass or signs of hormone production. Both may be associated with specific genetic syndromes. Staging for ovarian sex cord-stromal tumors is based on the International Federation of Gynecology and Obstetrics classification for ovarian carcinoma. Treatment for those with high risk disease includes multiagent chemotherapy. Testicular stromal tumors often, though not always, follow a benign course. Additional research will help to define optimal treatment strategies for children with these rare tumors.     

Primary Heart Tumors in the Pediatric Age Group: A Review of Salient Pathologic Features Relevant for Clinicians

Because primary tumors of the heart in infants and children are extremely rare, most knowledge is based on collections of case reports rather than large cohort studies. The types of heart tumors encountered in the pediatric age group differ from those seen in adults. In the latter, cardiac myxomas are by far the most common tumor; in infants and children the most common primary tumor of the heart is the rhabdomyoma. Spontaneous regression of these tumors has been well established so that surgical intervention is no longer indicated unless there are clinical manifestations from the heart. There is a high incidence of associated tuberous sclerosis. Any intracavitary mass in infants is suggestive for a cardiac rhabdomyoma unless otherwise proven. The second most common tumor in this age group is cardiac fibroma. These tumors probably represent hamartomatous lesions and this has led to a strategy in which radical surgical excision is not indicated if the procedure endangers postoperative heart function. Cardiac myxomas are of interest in this age group because of their familial occurrence as part of the myxoma syndrome. Other types of primary heart tumors occur, including malignant variants, but all are exceedingly rare. It is because of the sporadic nature of these tumors that treatment and insights into prognosis are based largely on case documentations and analogies from similar tumors originating elsewhere.     

Intracranial desmoid tumor with familial adenomatous polyposis coli

Intracranial desmoid tumors are extremely rare. The association of desmoid tumors with familial adenomatous polyposis coli was reported previously, with the tumors involving trunk and extremities. We report a 3.5-year-old girl with intracranial desmoid tumor with familial adenomatous polyposis coli. This condition in a child is rarely reported. Follow-up of the patient after cranial surgery and of the family for this premalignant inherited condition is necessary.     

Pediatric tumors of the eye and orbit

Most ocular and orbital tumors of childhood are distinct from tumors that occur in adults. Many are congenital with early presentations. Most pediatric orbital tumors are benign; developmental cysts comprise half of orbital cases, with capillary hemangioma being the second most common orbital tumor. The most common orbital malignancy is rhabdomyosarcoma. The most common intraocular malignant lesion is retinoblastoma. Choroidal melanoma, which is common in adults, is extremely rare in children. The orbit is the most common location for metastases in children, whereas the choroid is the predominant site in adults. Pediatricians play a vital role in diagnosis of pediatric ocular tumors. They are the first to recognize ocular problems that may not be apparent to parents. It is therefore important to recognize the signs and symptoms of ocular tumors of childhood so that prompt ophthalmologic evaluation and treatment may be undertaken. Whereas the malignant tumors may be life-threatening, both malignant and benign tumors may be vision-threatening.