Perinatal (fetal and neonatal) choroid plexus tumors: a review.

INTRODUCTION: The object of this review is to describe the choroid plexus tumors (CPTs) occurring in the fetus and neonate with regard to clinical presentation, location, pathology, treatment, and outcome. MATERIALS AND METHODS: Case histories and clinical outcomes were reviewed from 93 cases of fetal and neonatal tumors obtained from the literature and our own institutional experience from 1980 to 2016. RESULTS: Choroid plexus papilloma (CPP) is the most common tumor followed by choroid plexus carcinoma (CPC) and atypical choroid plexus papilloma (ACPP). Hydrocephalus and macrocephaly are the presenting features for all three tumors. The lateral ventricles are the main site of tumor origin followed by the third and fourth ventricles, respectively. CPTs of the fetus are detected most often near the end of the third trimester of pregnancy by fetal ultrasound. The extent of surgical resection plays an important role in the treatment and outcome. In spite of excellent survival, which is especially true in the case of CPP, surgical resection may carry significant risks in an immature baby. Given the neonatal low blood volume and increased vascularity of the tumors, there is potential risk for hemorrhage. Although advances in neurosurgical techniques have led to a greater degree of complete surgical resections, survival for the perinatal CPC group remains low even with multimodality therapies. CONCLUSION: Perinatal CPTs have variable overall survivals depending on degree of surgical resection and tumor biology. An increased understanding of the molecular features of these tumors may lead to improved therapies and ultimately survival.

Perinatal (fetal and neonatal) astrocytoma: a review.

INTRODUCTION: The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond. MATERIALS AND METHODS: One hundred one fetal and neonatal tumors were collected from the literature for study. RESULTS: Macrocephaly and an intracranial mass were the most common initial findings. Overall, hydrocephalus and intracranial hemorrhage were next. Glioblastoma (GBM) was the most common neoplasm followed in order by subependymal giant cell astrocytoma (SEGA), low-grade astrocytoma, anaplastic astrocytoma, and desmoplastic infantile astrocytoma (DIA). Tumors were detected most often toward the end of the third trimester of pregnancy. CONCLUSION: A number of patients were considered inoperable since their tumor occupied much of the intracranial cavity involving large areas of the brain. High-grade astrocytomas were more common than low-grade ones in this review. Fetuses and neonates with astrocytoma have a mixed prognosis ranging from as low as 20 % (GBM) to a high of 90 %. The overall survival was 47/101 or 46 %.

Fetal intracranial teratoma. A review.

A literature and institutional review of fetal intracranial teratomas yielded 90 tumors. The mean age at ultrasound diagnosis was 32 weeks, ranging from 21 to 41 weeks. Males and females were equally affected. The average, maximum tumor size was 10 cm, varying between 3.5 and 23 cm. Forty-two percent of patients died within the first week of life. Death rate was exceptionally high before 30 weeks gestation where almost half the affected fetuses expired. The overall survival rate for 90 fetuses with intracranial teratoma was only 7.8%.

Role of hypoxia inducible factor-1 in keratinocyte inflammatory response and neutrophil recruitment.

BACKGROUND: Hypoxia inducible factor-1 (HIF-1) is a major regulator of the cellular adaption to low oxygen stress and the innate immune function of myeloid cells. Treatment with the novel HIF-1 stabilizing drug AKB-4924 has been shown to enhance the bactericidal activity of keratinocytes as well as phagocytic cells. In this study, we sought to investigate the effect of pharmacological boosting of HIF-1 with AKB-4924 in keratinocytes and their contribution to the innate immune response. FINDINGS: Treatment with the novel HIF-1 stabilizing drug AKB-4924 can increase keratinocyte production of pro-inflammatory cytokines in vitro and enhance neutrophil recruitment in vivo. CONCLUSIONS: HIF plays an important role in cytokine production by keratinocytes and in neutrophil recruitment to the skin. The HIF-boosting drug AKB-4924 has the potential to enhance the immune response even in the complex environment of bacterial skin infections.

Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function.

Hypoxia-inducible factor (HIF)-1α is a master regulator of inflammatory activities of myeloid cells, including neutrophils and macrophages. These studies examine the role of myeloid cell HIF-1α in regulating asthma induction and pathogenesis, and for the first time, evaluate the roles of HIF-1α and HIF-2α in the chemotactic properties of eosinophils, the myeloid cells most associated with asthma. Wild-type (WT) and myeloid cell-specific HIF-1α knockout (KO) C57BL/6 mice were studied in an ovalbumin (OVA) model of asthma. Administration of the pharmacological HIF-1α antagonist YC-1 was used to corroborate findings from the genetic model. WT, HIF-1α, and HIF-2α KO eosinophils underwent in vitro chemotaxis assays. We found that deletion of HIF-1α in myeloid cells and systemic treatment with YC-1 during asthma induction decreased airway hyperresponsiveness (AHR). Deletion of HIF-1α in myeloid cells in OVA-induced asthma also reduced eosinophil infiltration, goblet cell hyperplasia, and levels of cytokines IL-4, IL-5, and IL-13 in the lung. HIF-1α inhibition with YC-1 during asthma induction decreased eosinophilia in bronchoalveolar lavage, lung parenchyma, and blood, as well as decreased total lung inflammation, IL-5, and serum OVA-specific IgE levels. Deletion of HIF-1α in eosinophils decreased their chemotaxis, while deletion of the isoform HIF-2α led to increased chemotaxis. This work demonstrates that HIF-1α in myeloid cells plays a role in asthma pathogenesis, particularly in AHR development. Additionally, treatment with HIF-1α inhibitors during asthma induction decreases AHR and eosinophilia. Finally, we show that HIF-1α and HIF-2α regulate eosinophil migration in opposing ways.

Cutaneous metastases in neonates: a review.

Two hundred eight neonates with malignant tumors and cutaneous metastases were reviewed. Malignancies most often associated with cutaneous metastases, in order of rank, were leukemia, multisystem Langerhans cell histiocytosis, neuroblastoma, rhabdoid tumor, rhabdomyosarcoma, primitive neuroectodermal tumor, choriocarcinoma, and adrenocortical carcinoma. Bluish skin nodules producing the "blueberry muffin baby"-like appearance were the most common dermatologic finding in 171, or 82% of 208 neonates. The tendency of newborns to present with skin nodules is one of the significant differences between malignancies in younger and older children. Patients with rhabdoid tumor and rhabdomyosarcoma had the lowest survival rates, 4% and 15%, respectively, compared with leukemia, 37.5%, and neuroblastoma, 58%. Overall survival was 39%.

Fetal and neonatal rhabdoid tumor.

PURPOSE: Few studies have focused on the behavior of rhabdoid tumor (RT) in the fetus and neonate. The purpose of this review is to show that perinatal RTs are associated with unusual findings and a poor prognosis. METHODS: The author conducted a 40-year systematic review of the literature. Clinical presentation, pathology, management, and outcome of 72 fetuses and neonates with RTs are discussed. RESULTS: Seventy-two fetuses and neonates presented with RTs detected prenatally (n = 12) and during the neonatal period (n = 60). The review consisted of 3 main groups: extrarenal noncentral nervous system (CNS) RT, renal RT, and CNS RT. There were some group differences in survival: extrarenal non-CNS RT (3/33 or 9.1%), renal RT (2/27 or 7.4%), and CNS RT (2/12 or 16.7%). Metastatic RT was present at diagnosis in more than half the patients (41/72 or 57%) who had a survival of 2.3%. The overall survival was 9.7%. For statistical results, there was no significant difference in survival among the 3 groups by type of tumor (P = .692). chi(2) analysis for survival with and without metastases was not valid due to small sample size. CONCLUSIONS: The review shows that extrarenal RT was more common than either renal RT or CNS RT groups that is different than that observed in older individuals. Concomitant brain tumors were found in almost a third of fetuses and neonates. The CNS involvement occurred more often in patients with renal RT than in those with extrarenal RT. Metastatic disease at diagnosis was noted in more than half of the patients. Higher stage and presence of a CNS tumor were significant determinants in survival.

Fetal and newborn adrenocortical tumors.

Adrenocortical tumors occur less often in the fetus and newborn than later in life. The purpose of this study was to focus on the fetus and newborn in an attempt to determine the various ways these tumors differ in their biologic behavior, pathology, clinical presentation and response to therapy from those occurring in the older child and adolescent. Twenty-five fetuses and newborns were diagnosed with ACTs prenatally (n = 3) and in the newborn period (n = 22). The study consisted of two main neoplasms: adrenocortical adenoma, 24%, and adrenocortical carcinoma, 76%. The most common presenting finding was an abdominal mass. Overall survival for patients with ACA and ACC were 33% and 53%, respectively.

Perinatal neurofibromatosis: two case reports and review of the literature.

Neurofibromatosis-1 (NF-1) is an autosomal-dominant genetic disorder with many different manifestations. Some may have evidence of the disease at birth. A 66-year (1942 to 2008) retrospective review of 36 patients including 7 fetuses and 29 neonates with NF-1 was performed. Only patients with NF-1 lesions detected before birth by imaging or noted in the first month of life were entered into the review. There was a strongly positive family history of the disease of 70%. The most common presenting findings in the fetus were hydrops, macrocephaly, and thickened neck soft tissues and those in the neonate were café au lait macules, skin nodules, and buphthalmos. Survivors developed serious sequelae (e.g., progressive growth of neurofibromas within the neck and mediastinum leading to increasing airway obstruction and death; an enlarging, proptotic, and glaucomatous eye; and occurrence of brain and malignant nerve sheath tumors). Congenital generalized (disseminated) neurofibromatosis was associated with a poor prognosis, with a mortality rate of 92%. Survival rates for patients detected before and after birth were 28% and 62%, respectively. The overall survival was 20/36 or 56%.

Perinatal (fetal and neonatal) tuberous sclerosis: a review.

Tuberous sclerosis (TSC) is an autosomal-dominant disorder that presents with highly variable clinical manifestations including seizures, mental retardation, skin lesions, and hamartomas affecting multiple organ systems such as the heart, brain, eye, and kidney. A 42-year retrospective review of 70 patients consisting of 43 fetuses and 27 neonates with TSC were analyzed. There was a 16% positive family history for the disease. Obvious signs are present in the perinatal period. Cardiac rhabdomyoma(s) detected on routine antenatal sonography, arrhythmias, cerebral lesions, hydrops, and stillbirth are the major presenting findings in the fetus, whereas respiratory distress, arrhythmias, murmurs, and cardiomegaly are the main signs initially in the neonate. Cardiac rhabdomyomas comprised 32.8% of the TSC pathological findings; those of central nervous system origin, 47.5%; and renal cystic disease, 13.2%. Skin lesions and retinal hamartomas were noted rarely at birth. Of the 15 survivors, 87% developed a seizure disorder; 33%, residual cardiac rhabdomyomas; and 27%, mental retardation. The survival rates of patients diagnosed antenatally was practically the same as for those after birth, 21% and 22%, respectively. The overall survival was low, 15/70 or 21%. When TSC occurs in the perinatal period, it is associated with a high incidence of morbidity and mortality.

Fetal brain tumors: a review of 154 cases.

The purpose of this literature review is to describe the various types of brain tumors that occur in the fetus, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond. An analysis is performed on patients with fetal brain tumors that were detected prenatally by imaging studies or discovered directly after birth. The review revealed 154 fetuses presenting with brain tumors. Teratoma was the leading neoplasm. Next was astrocytoma followed by craniopharyngioma, primitive neuroectodermal tumor, choroid plexus papilloma, meningeal tumors, and ependymoma. The most common presenting findings were macrocephaly and an intracranial mass. Overall hydrocephalus was next, followed by stillbirth. Most tumors were detected during the third trimester of pregnancy. Over a third of the affected fetuses were stillborn. Many tumors were inoperable as they occupied much of the intracranial cavity and involved large areas of the brain. Overall survival rate was 23/154, or 15%. Generally fetal brain tumors are associated with a poor prognosis.

Fetal and neonatal renal tumors.

This is a review of renal tumors diagnosed between 1960 and 2007 in 47 fetuses and 163 infants less than 2 months old. There were 139 congenital mesoblastic nephromas, 41 Wilms' tumors, 23 rhabdoid tumors of the kidney, and 7 clear cell sarcomas of the kidney. The initial clinical manifestations, staging, management, and outcome of these patents are summarized in the tables and text.

Fetal hydrops associated with tumors.

Fetuses with tumors associated with hydrops have a high mortality rate. Relatively few survivors have this potentially fatal combination. This study examined the clinical and pathological findings, pathogenesis, and outcomes of fetuses with tumors and hydrops. One hundred and fifty-eight study cases were collected from the literature and from personal files. Only patients where adequate clinical and pathological data were given and the outcome of pregnancy was described were included in the study. Cardiac tumors were the majority found in association with fetal hydrops. Leukemia and extracardiac teratomas were next in frequency followed by hepatic tumors, neuroblastoma, placental, soft tissue, and renal tumors. The main presenting findings along with hydrops were hydramnios, a tumor mass, placentomegaly, and stillbirth. Most tumors were detected in the third trimester of pregnancy. No fetus with the diagnosis of cardiac rhabdomyoma, neuroblastoma, brain tumor, rhabdoid tumor, or histiocytosis associated with hydrops survived. Those patients with placental chorangioma, pericardial teratoma, and hepatic hemangioma had the best outcome. The overall survival rate was low: 30 of 158 (19%).

Fetal and neonatal neuroblastoma: retrospective review of 271 cases.

Neuroblastoma is the foremost malignant neoplasm of the fetus and neonate. The tumor is unique because of its distinctive biologic behavior and many different clinical manifestations. The purpose of this review is to focus on the fetus and neonate to determine the various ways perinatal neuroblastomas differ clinically and morphologically and in their treatment from those found in the older child to show that some forms of the tumor have a better outcome than others. The report attempts to evaluate the influence of site, histology, stage, biologic markers, and treatment on survival.

Fetal and neonatal hepatic tumors.

BACKGROUND/PURPOSE: Although hepatic tumors are uncommon in the perinatal period they are associated with significant morbidity and mortality in affected patients. The purpose of this review is to focus on the fetus and neonate in an attempt to determine the various ways liver tumors differ clinically and pathologically from those found in the older child and adult and to show that certain types of tumors have a better prognosis than others. METHODS: The author conducted a retrospective review of perinatal hepatic tumors reported in the literature and of patients treated and followed up at Children's Hospital San Diego and Children's Hospital Los Angeles. Only fetuses and infants younger than 2 months with adequate clinical and pathologic data ere accepted for review. The period of patient accrual was from 1970 to 2005. Length of follow-up varied from 1 week to more than 5 years. Elevated alpha-fetoprotein level was defined as one significantly higher than that of the reporting institution's normal level for age group; laboratory values for this protein vary from one institution to the next and therefore it was not possible to assign one figure as a standard reference number. Discussion of the differential diagnosis and pathologic findings of hepatic tumors in the fetus and neonate are described elsewhere and will not be discussed here in detail (Perspect Pediatr Pathol 1978;4:217; Weinberg AG, Finegold MJ. Primary hepatic tumors in childhood. In: Finegold M, editor. Pathology of neoplasia in children and adolescents. Philadelphia, PA: WB Saunders, 1986; Am J Surg Pathol 1982;6:693; Pediatr Pathol 1983;1:245; Arch Surg 1990;125:598; Semin Neonatol 2003;8:403; Pediatr Pathol 1985;3:165; Isaacs H Jr. Liver tumors. In: Isaacs H Jr, editor. Tumors of the fetus and newborn. Philadelphia, PA: WB Saunders, 1997; Isaacs H Jr. Liver tumors. In: Isaacs H Jr, editor. Tumors of the fetus and infant: an atlas. Philadelphia, PA: WB Saunders, 2002). RESULTS: One hundred ninety-four fetuses and neonates presented with hepatic tumors diagnosed prenatally (n = 56) and in the neonatal period (n = 138). The study consisted of 3 main tumors: hemangioma (117 cases, 60.3%), mesenchymal hamartoma (45 cases, 23.2%), and hepatoblastoma (32 cases, 16.5%). The most common initial finding was a mass found either by antenatal sonography or by physical examination during the neonatal period. Overall, hydramnios was next followed by fetal hydrops, respiratory distress, and congestive heart failure, which were often related to the cause of death. Half of the fetuses and neonates with hepatoblastoma had abnormally elevated serum alpha-fetoprotein levels compared with 16 (14%) of 117 of those with hemangioma and 1 neonate with mesenchymal hamartoma. There were 76 (65%) examples of solitary (unifocal) hemangiomas and 41 (35%) of multifocal (which included the entity diffuse hemangiomatosis) with 86% and 71% survival rates, respectively. Of 45 patients with mesenchymal hamartoma, of the 29 (64%) who had surgical resections, 23 (79%) survived. Patients with hepatoblastoma had the worst outcome of the group, for only 8 (25%) of 32 were alive. Half of patients with either stage 1 or 3 hepatoblastoma died; no patient with stage 4 survived. There was some relationship between histologic type and prognosis. For example, half of the patients with the pure fetal hepatoblastoma histology survived compared with those with fetal and embryonal histology where 30% survived. Fifteen of 32 hepatoblastoma patients received surgical resection with or without chemotherapy, resulting in 7 (47%) of 15 cures. The 56 fetuses and 138 neonates with hepatic tumors (hemangioma, mesenchymal hamartoma, and hepatoblastoma) had survival rates of 75%, 64%, and 25%, respectively. The overall survival of the entire group consisting of 194 tumors was 125 or 64%. CONCLUSIONS: The study shows that clinical findings in fetuses and neonates with hepatic tumors are less well defined than in older children. Survival rates are much lower as well. When the clinical course is complicated by associated conditions such as stillbirth, fetal hydrops, congestive heart failure, severe anemia, or thrombocytopenia, the mortality rate is much greater. If the patient is mature enough and in a clinical condition where he or she can be operated on, survival figures approach those of the older child. Some hepatic tumors have a better prognosis than others. Neonates with focal (solitary) hepatic hemangiomas have the best outcome and fetuses with hepatoblastoma the worst. Although infantile hemangioma undergoes spontaneous regression, it may be life threatening when congestive heart failure and/or consumptive coagulopathy occur. Mesenchymal hamartoma is a benign lesion best treated by surgical resection, which usually results in cure. However, there are fatal complications associated with this tumor, ie, fetal hydrops, respiratory distress, and circulatory problems owing to a large space occupying abdominal lesion and sometimes stillbirth, all contributing to the death rate. Hepatoblastoma, the major malignancy of the fetus and neonate, is treated primarily by surgical resection. Pre- or postoperative chemotherapy is reserved for those patients with unresectable tumors or metastatic disease. The survival rate is much lower than that reported by multigroup prospective trials. Patients die from the mass effect caused by the tumor, which lead to abdominal distension, vascular compromise, anemia, hydrops, respiratory distress, and stillbirth. Metastases to the abdominal cavity, lungs, and placenta are other causes of death. Because of the danger of labor-induced rupture of the tumor and potentially fatal intraabdominal hemorrhage, cesarean delivery is recommended when a hepatic tumor is found on prenatal ultrasound.

Fetal and neonatal histiocytoses.

PURPOSE: The histiocytoses are a group of disorders of the monophagocytic system having a variety of clinical and pathological findings. They occur less often during the perinatal period than later in life. Their biologic behavior, response to therapy, and histologic types are not the same. METHODS: The study consisted of 221 fetuses and neonates collected from the literature and from personal files. RESULTS: Langerhans' cell histiocytosis (LCH), the hemophagocytic lymphohistiocytoses (HLH), and juvenile xanthogranuloma (JXG), in order of rank, were the main histiocytoses occurring in the perinatal period. HLH accounted for the highest mortality (74%) followed by disseminated LCH (52%) and JXG (11%). All neonates with LCH and JXG limited to the skin and/or subcutaneous tissue survived with or without treatment. CONCLUSIONS: This study suggests that there is an increased incidence of spontaneous regression of certain histiocytic lesions in neonates as compared to older individuals. Cutaneous forms JXG and LCH had the highest incidence of regression followed by infection associated HLH.

Tumors associated with sudden infant and childhood death.

Tumors are rare causes of sudden death in infancy and early childhood. The goals of this study were to determine the types and frequency of the tumors associated with sudden death occurring in cases between birth and age 3 years. The San Diego Sudden Infant Death Syndrome/sudden unexplained death in childhood (SUDC) Research Project database and the literature were reviewed retrospectively. Sixty-eight cases, with the most (84%) affecting the heart and brain, were identified. Tumors are a rare but significant cause of sudden death in infancy and early childhood, and their diagnosis may have significant genetic implications for planning future pregnancies. The diagnosis of these lesions can be established only after thorough postmortem examination.

Perinatal (fetal and neonatal) germ cell tumors.

BACKGROUND/PURPOSE: Germ cell tumors are relatively common in the fetus and neonate and are the leading neoplasms in some perinatal reviews. The purpose of this study is to focus on the fetus and neonate in an attempt to determine the various ways germ cell tumors differ clinically and morphologically from those occurring in the older child and adult and to show that certain types of tumors have a better prognosis than others. METHODS: The author conducted a retrospective review of perinatal teratomas and other germ cell tumors reported in the literature and of patients treated and followed up at Children's Hospital San Diego and Children's Hospital Los Angeles. Only fetuses and infants less than 2 months of age with adequate clinical and pathologic data were accepted for review. RESULTS: Five hundred thirty-four fetuses and neonates presented with teratomas diagnosed prenatally (n = 226) and at birth (n = 309). The most common initial finding was a mass, noted either by antenatal sonography or by physical examination during the neonatal period, with signs and symptoms referable to the site of origin. Overall polyhydramnios was next followed by respiratory distress and stillbirth. The number of mature and immature teratomas was approximately the same. The incidence of teratoma with yolk sac tumor either at presentation or at recurrence was 5.8%, and the survival rate was 39%. Sacrococcygeal teratomas had the highest incidence of yolk sac tumor at 10%. Recurrent disease in the form of either teratoma or yolk sac tumor developed in 5% of patients. All individuals with teratomas who survived received surgical resection. CONCLUSIONS: Some germ cell tumors of the fetus and neonate have a better prognosis than others. Neonates with gastric teratomas have the best survival rates, and those with intracranial germ cell tumors the worst. Fetuses with teratomas detected antenatally have 3 times the mortality rate compared with postnatally diagnosed neonates. Although perinatal teratomas have a relatively low recurrence rate of 5%, close follow-up with imaging studies and serum alpha-fetoprotein determinations is is strongly recommended. Surgical resection alone may be adequate therapy for teratomas with nonmetastatic, microscopic foci of yolk sac tumor. In the nonteratoma group, patients with pure yolk sac tumor and gonadoblastoma have a much better outcome than those with choriocarcinoma, which has a very low survival of rate of 12%. Currently, the use of platinum-based combination chemotherapy has significantly improved the survival rate of infants with advanced malignant germ cell tumor disease.

Fetal and neonatal leukemia.

The biological and clinical characteristics of perinatal leukemia differ significantly from those of leukemia in older children, and the prognosis is generally bleak. Once complete remission is achieved, neonates with acute myelocytic leukemia (AML) fare much better than those with acute lymphocytic leukemia (ALL). The results of this study suggest that age, sex, type of leukemia, and cytogenetic findings have a strong influence on outcome. Neonates, particularly females, with pre-B ALL have a much worse prognosis than neonates and older children with this disease. Transient leukemia in the Down syndrome neonate is associated with significant morbidity; close follow-up is recommended for at least the first 3 years of life because of the potential of developing acute leukemia, particularly AMKL (M7). The purpose of this review is to focus on the fetus and neonate in an attempt to determine the various ways leukemia differs clinically and morphologically from the disease occurring in older infants and children and to demonstrate that certain types of leukemia have a poor prognosis compared with those occurring in older children.