- Open Access
Congenital tumors: imaging when life just begins
© European Society of Radiology 2011
- Received: 18 August 2010
- Accepted: 27 January 2011
- Published: 14 February 2011
The technical developments of imaging methods over the last 2 decades are changing our knowledge of perinatal oncology. Fetal ultrasound is usually the first imaging method used and thus constitutes the reference prenatal study, but MRI seems to be an excellent complementary method for evaluating the fetus. The widespread use of both techniques has increased the diagnosis rates of congenital tumors. During pregnancy and after birth, an accurate knowledge of the possibilities and limits of the different imaging techniques available would improve the information obtainable, thus helping the medical team to make the most appropriate decisions about therapy and to inform the family about the prognosis.
In this review article, we describe the main congenital neoplasms, their prognosis and their imaging characteristics with the different pre- and postnatal imaging methods available.
- Pediatric oncology
- Prenatal diagnosis
- Fetal US
- Fetal MRI
- Neonatal imaging
Tumors are considered congenital when detected during pregnancy or in the first 3 months of life [1, 2]. Congenital tumors represent only 1.5–2% of all pediatric tumors, with a prevalence of 1:12,500 to 1:27,500 live births [3–5]. Recent studies demonstrate an increase in the incidence of congenital tumors , probably as a consequence of both the generalization of routine prenatal and neonatal medical controls and of the improvement of prenatal imaging techniques.
Over the last few years, we have witnessed significant technical improvements in prenatal imaging diagnostic tools. Ultrasound is usually the first imaging method used, but antenatal magnetic resonance imaging (MRI) is increasingly being used as a complementary study. Standard postnatal imaging methods include conventional X-ray, ultrasound, CT and MRI.
The purposes of this review are to describe the most frequent types of congenital tumors and their prognosis, to review the main imaging characteristics of this heterogeneous group of neoplasms, and to define the role of the different pre- and postnatal imaging methods in the characterisation of congenital tumors, with special emphasis on prenatal MRI.
Extracranial teratomas are neoplasms derived from the primordial germ cells. They may contain components arising from all three germ layers and therefore may present different tissue types. Most congenital teratomas are histologically benign and typically located mid-line. The main location of these tumors is the sacrococcygeal region (45% of cases), followed by the cervicofacial area (28%) and the thorax (11%) .
Cervicofacial teratomas (Fig. 1c, d) have an incidence of 1:40,000 to 1:80,000 live births. They may originate in different anatomical structures, including the orbit, the naso- and oropharynx, the tongue, the palate and the anterior neck . Cervical teratomas in utero may not only cause hydrops secondary to fetal swallowing disturbances, but also fetal pulmonary hypoplasia. Large tumors may cause hyperextension of the fetal neck with resulting dystocia . Ex utero intrapartum treatment, or EXIT, has been performed in recent years in cases of giant neck masses in highly specialized neonatal medical centers, improving the initial fetal survival [21, 22].
Thoracic teratomas originate mainly in the pericardium . Pericardial effusion is typically present and may lead to life-threatening tamponade. Indeed, in cases of fetal pericardial effusion, teratoma should be seriously considered in the differential diagnosis. Pericardiocentesis can help to prevent fetal death. Mediastinal teratomas are rare. They should be removed after birth to prevent malignant degeneration .
The neuroblastoma is the second most common pediatric malignancy overall, after teratoma, in most published series [3, 5] and the most common malignancy of the first month of life (30–50%] . The tumor arises from primordial neural crest cells, anywhere along the sympathetic chains, at the adrenal medulla (Fig. 2b), the extra-adrenal retroperitoneum (Fig. 2c, d) or the posterior mediastinum.
Fetal neuroblastoma is usually detected during the third trimester of pregnancy. It is mostly of adrenal origin (90% of cases). The prognosis is excellent, with a survival rate of 88–90% [1, 24], metastases are rare and spontaneous involution in utero has been described. On ultrasound, the tumor is mostly seen as a solid, heterogeneous echogenic mass that displaces the adjacent kidney inferiorly and laterally. Cystic tumors are often seen and have an excellent prognosis . Calcifications are present in 30% of all cases. On MRI, neuroblastomas are typically heterogeneous, with relatively low signal intensity on T1- and high signal intensity on T2-weighted images. Cystic changes appear as bright areas on T2-weighted images .
Neonatal neuroblastomas are of adrenal origin in 45% (Fig. 2b) and of extra-adrenal origin in 55% of all cases (Fig. 2c, d]. Although often metastatic [60% of cases, principally liver (Fig. 2c), bone and skin], it has an overall survival rate of 64% [1, 24]. On CT, the tumor is heterogeneous, with calcifications, necrosis and areas of hemorrhage. Extension into the spinal canal is seen in 10% of abdominal (Fig. 2d) and in 28% of thoracic masses, and is clearly visualized on MRI studies . Metaiodobenzylguanidine (MIBG-I123) scintigraphy is an excellent method for determining the presence of metastases or tumor recidivation, but 30% of neonatal tumors are MIBG-negative .
The International Neuroblastoma Staging System  is mainly based on the degree of surgical resection and shows some difficulties for application in congenital cases. Recently, a new International Neuroblastoma Risk Group Staging System (INRGSS), based on imaging findings, was designed to stage the patients at the time of diagnosis. In this classification, the extent of locoregional disease is determined by the absence (L1) or presence (L2) of imaging-defined risk factors , with stage M used for widely disseminated disease and stage MS for metastatic disease limited to liver, skin and bone narrow in children younger than 18 months . The main role of imaging methods for both fetal and neonatal neuroblastoma is then to determine the origin of the mass, its locoregional extent and the presence or not of metastases for staging before therapy.
Congenital soft-tissue tumors constitute a heterogeneous group of lesions, including mainly vascular and muscular tumors. The International Society for the Study of Vascular Anomalies (ISSVA) differentiates between vascular tumors and vascular malformations (capillary, venous, lymphatic or mixed) , which are not discussed in this review.
The notion of congenital hemangiomas has been introduced recently, differentiating between non-involuting congenital hemangiomas, or NICH, and rapidly involuting congenital hemangiomas, or RICH . Although both RICH and NICH groups show similar imaging findings to IH on ultrasound, they may also present vascular aneurysms, intravascular thrombi and arteriovenous shunting, features not usually observed in IH . Large congenital tumors may cause compression of vital structures or cardiovascular complications, and in these cases, MRI is the method of choice to determine the mass extension and its relationship to the adjacent anatomical structures (Fig. 3c, d). Hemangiomas are usually hyperintense on T2-weighted and isointense on T1-weighted images related to muscle, with prominent draining veins  and intense enhancement after contrast medium administration , but no perilesional edema.
Fibrous connective tissue tumors are the largest group of congenital soft-tissue tumors. Fibromatosis and myofibromatosis are rare benign disorders with a tendency to infiltrate adjacent tissues but no metastases. They present an increment of the size and the number of lesions during the first year of life with later regression. The ultrasound shows a soft-tissue mass with variable echogenicity. They are muscle isodense and poorly defined on CT (Fig. 3d), with low signal intensity on both T1-weighted and T2-weighted images , infiltration of the fat and muscle, and intense enhancement after i.v. contrast medium injection on MRI. The malignant variant is the congenital infantile fibrosarcoma .
Rhabdomyosarcoma arises from the embryonic mesenchyme with the potential to differentiate into skeletal muscle. The tumor represents >50% of all soft tissue sarcomas in children, but its congenital presentation is extremely rare . It can arise in any anatomical region of the body (except bone) whether there is skeletal muscle or not, but most often it presents in the head and neck (28–40%) and in the genitourinary region (20%). The ultrasound shows a soft-tissue mass, similar to muscle, whereas MRI reveals a mass isointense to muscle on T1-weighted and hyperintense on T2-weighted images, with heterogeneous enhancement after gadolinium administration. Some previously classified congenital rhabdomyosarcomas with a bad outcome were probably unrecognized rhabdoid tumors. Immunochemistry tests show that rhabdoid tumors typically lack staining for BAF47 in tumor cells because of a clonal mutation in the INI1 gene . This anomaly now allows correct differentiation between rhabdoid tumors—usually associated with a bad prognosis—and rhabdomyosarcomas .
The main role of imaging in the case of congenital soft tissue tumors is to determine the extent of the mass and to identify the invasion of adjacent structures in order to optimize the surgical approach.
Congenital tumors of the central nervous system (CNS) are rare. They have a poor prognosis with an overall mortality of 72% [37–41]. They represent only 0.5–1.9% of all pediatric brain tumors, but are responsible for 5–20% of deaths secondary to neoplasms in this age group [6, 38].
Teratoma is the most common congenital brain tumor and represents 26.6 to 48% [38–41] (Table 2). Congenital teratomas are predominantly supratentorial, with the cerebral hemispheres being the main primary site, followed by the third ventricle and the pineal region . On ultrasound, they are seen as typically large, mid-line heterogeneous tumors with solid areas replacing much of the brain. Cystic components are often found  and probably represent necrotic areas in tumors with a rapid growth rate. Calcifications are possible, but unusual.
The astrocytoma is the most common neuroglial tumor. The cerebral hemispheres are the main primary site, followed by the optic nerve, the thalamus and the mesencephalus. They typically present with macrocephaly. Fetal ultrasound and MRI show a solid tumor replacing the normal brain parenchyma. Hemorrhage is common.
Primitive neuroectodermal tumors (PNET) (Fig. 4c, d) are small-cell malignant tumors arising from the neural crest . The most common locations are the cerebellum and the cerebral hemispheres. Congenital tumors have a poor prognosis as a consequence of the rapid tumor growth, with early extension throughout the CSF pathways.
The diagnosis of fetal and neonatal brain tumors is associated with high mortality rates (Table 2). Recent advances in MRI technology include the development of magnetic resonance diffusion sequences (DWI), which may identify areas of restricted water movement and of magnetic resonance spectroscopy (MRS), which recognizes changes in metabolite concentration . These technical improvements have opened up exciting perspectives, suggesting the possibility of differentiating between histological tumor types [20, 45], but preliminary reports have not yet been confirmed for congenital brain tumors. The main role of imaging studies is still to determine the extent of the tumor in order to evaluate therapy challenges and to identify potentially curable tumors, such as plexus papillomas, differentiating them from rapidly fatal ones.
Renal tumors represent 5–7.1% of all congenital tumors (Table 1). They are mostly benign, with the most frequent histological types being mesoblastic nephroma (MSN), nephroblastomatosis and the multilocular cystic nephroma . Wilms’ tumor and renal rhabdoid tumors are rare in neonates [1, 14, 46].
Nephroblastomatosis consists of diffuse, multifocal nephrogenic rests in the kidneys. It is found incidentally in 1% of normal children at post-mortem studies and may cause a Wilms’ tumor in 30–40% of the cases (Fig. 5c). There is a well-known association with Beckwith-Wiedemann syndrome, trisomy 18 and sporadic aniridia . Typical ultrasound images show multifocal, subcapsular renal nodules, hypo- or isoechoic, related to renal parenchyma. The nodules present low attenuation on CT and low signal intensity on both T1- and T2-weighted images on MRI relative to normal parenchyma, with reduced contrast enhancement.
Multilocular cystic nephroma (MCN) is a benign cystic renal neoplasm, arising from metanephric blastema. Imaging shows a large multilocular cystic renal mass, with septa as the only solid component (Fig. 5d). Septa may enhance after contrast medium administration. Metastatic disease has not been reported.
The role of imaging studies for congenital renal tumors is to determine the extent of the mass and its relationship to the renal vascular structures before surgical therapy.
Hepatic tumors comprise 5% of all congenital neoplasms (Table 1). Excluding metastases, principally from leukemia and neuroblastoma , most primary hepatic tumors are hemangiomas (60.3%), followed by mesenchymal hamartoma (23.2%) and hepatoblastoma (16.5%) .
The mesenchymal hamartoma is a developmental cystic tumor, resulting from the benign overgrowth of mature hepatic tissue, with variable loose mesenchyme. Association with Beckwith-Wiedemann syndrome has been reported. Ultrasound shows a tumor composed of variably sized anechoic cysts with internal septations. Solid tumors have been described, but they are atypical [47, 51]. On MRI the cysts are fluid isointense lesions with septa and stromal components (Fig. 6c) .
Congenital hepatoblastoma is a malignant embryonic tumor composed of only epithelial cells or a mixture of epithelial and mesenchymal cells. They present as lobulated, sometimes multifocal large solid masses, most often in the right hepatic lobe (60%). An association with hemihypertrophy (2%), Beckwith-Wiedemann and intestinal polyposis is well established. The α-fetoprotein may be negative in a considerable percentage of fetal and neonatal tumors . Ultrasound shows a well-defined, solid mass (Fig. 6d), often with a spoked-wheel appearance. The lesion is heterogeneous, with calcifications (50%), cystic and necrotic areas . CT and MRI show a heterogeneous solid hepatic lesion with non-uniform enhancement.
The differential diagnosis of congenital hepatoblastoma is the malignant hepatic rhabdoid tumor. The most extensive published series about congenital hepatic tumors describes a poor prognosis for hepatoblastomas, with common early metastases and high mortality rates , but this series probably includes some cases of congenital rhabdoid tumors, an aggressive lesion previously classified as hepatoblastoma with negative α-fetoprotein. As mentioned elsewhere in this article, immunochemistry tests for INI1/BAF47 protein, which is abnormally low in all rhabdoid tumors, have recently allowed a correct differentiation between the entities [36, 37, 53, 54], which present similar findings on imaging studies.
The main role of imaging methods for congenital hepatic tumors is to evaluate the anatomical extent of the tumor and to clarify the relationship with hepatic lobar anatomy before surgical planning.
The heart is one of the most common organs of origin of congenital tumors, with a reported incidence of 0.14 to 0.2% . The incidence has been increasing in recent years because of the technical advances of imaging studies, especially ultrasound cardiography and cardiac MRI. Cardiac tumors may be related to genetic disorders such as neurofibromatosis, Beckwith-Wiedemann syndrome, familial myxoma syndrome and tuberous sclerosis. Most fetal and newborn cardiac tumors are benign. The most frequent cardiac tumor is the myocardial rhabdomyoma (78%), followed by the pericardial teratoma (18%) and the cardiac fibroma (12%) . Pericardial teratoma has already been described in this article.
Pleuropulmonary congenital neoplasias are extremely rare. The pleuropulmonary blastoma is a primary mesenchymal neoplasm with a very poor prognosis. On prenatal ultrasound and MRI, it presents as a solid heterogeneous mass originating from the pleura or the pulmonary parenchyma (Fig. 7b), often with additional pleural effusion (Fig. 7c). After birth, the tumor may manifest as a benign-appearing, air-filled cystic lesion or as large heterogeneous solid masses. The main differential diagnoses include the rhabdomyosarcoma and the undifferentiated sarcoma.
Congenital tumors are a unique, heterogeneous group of neoplasms that differ in many aspects from tumors presenting later in life. Congenital fetal and neonatal neuroblastomas are associated with a better prognosis than tumors detected later in life, but they remain an exception. Although mostly benign, the therapeutic possibilities of most congenital tumors may be limited because of the tumor size, its location or the stage of the pregnancy at the time of diagnosis. Moreover, the low incidence and the great histological diversity of these tumors reduces the number of published articles about them. Indeed, most of the published reference series are retrospective studies, including cases diagnosed and treated for the last 20–30 years and giving mortality values that are far away from actual reality in pediatric hospitals [2, 3, 10–14]. Although prediction of the possible prognosis and postnatal outcome is complicated, perinatal, anesthetic and surgical care is constantly improving nowadays such that more infants survive in general.
In recent years, imaging methods have acquired a relevant role in the diagnosis of fetal tumors. Ultrasound is the standard method for fetal evaluation: it is ideal for screening, safe for mother and child, widely accessible and relatively inexpensive, but its effectiveness may be limited by factors such as oligoamnios, maternal body habitus, fetal position and fetal shadow bone artifacts. Prenatal MRI is increasingly being used as a complementary imaging technique, but its real utility for congenital tumors has not yet been widely evaluated. In general, fetal MRI should only be performed if it is considered that additional results might influence the management of the pregnancy and/or the therapeutic approach. Recent articles have shown a more accurate evaluation of MRI compared with ultrasound in some cases of congenital tumors, including the local anatomical extent of sacrococcygeal and cervicofacial teratomas, which may be underestimated on ultrasound because of fetal bone shadowing [18, 23]. MRI may also discriminate between cystic and hemorrhagic areas with T1 or T2* sequences, information that may be relevant for evaluating the therapeutic challenges for SCT [18, 23] and some intracranial tumors. MRI also seems to be better in the evaluation of the deep extension of large tumors that do not always respect anatomical planes, such as hemangiomas or cervicofacial teratomas [20, 32]. Moreover, MRI allows a complete examination of the spinal canal in paravertebrally located tumors, such as neuroblastomas or SCT . Finally, MRI performed during late pregnancy provides excellent anatomical details in a safe intrauterine environment, which may delay the need for immediate postnatal imaging.
Brain tumors are a special group of congenital neoplasms. The detection of a congenital brain tumor in a fetus is followed by serious ethical considerations about the real prognosis, postnatal quality of life, therapy challenges and long-term consequences of the applied therapy. The low incidence, great diversity and different behaviors of congenital brain tumors compared with tumors in older patients mean that published results, obtained from older children and adults, cannot be directly extrapolated. Overall prognosis is poor and therapeutic options limited, with an evident discrepancy between our diagnostic capacities and our therapy possibilities. A confident identification of the individual tumor types based on imaging is almost impossible, and therefore, in countries in which a legal medical interruption of pregnancy is possible, this diagnosis may lead to a high rate of legal abortions .
In conclusion, ultrasound and MRI have increased the rate of detection of congenital tumors in prenatal life. During pregnancy and after birth, the main role of imaging is to provide accurate information about the origin and the extent of the tumor, the invasion of adjacent organs, and the presence or absence of metastasis. This information is crucial for reducing the differential diagnosis and to evaluate and optimize the pre- and postnatal therapeutic challenges. A correct knowledge of the possibilities of the different imaging techniques in fetal and neonatal studies would improve all obtainable information, helping the medical team to make the most appropriate decisions about therapy. Prenatal ultrasound remains the standard diagnostic method, but fetal MRI seems to be an excellent complementary imaging technique, and its real utility should be evaluated in larger, multicentric series.
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