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From the Archives of the AFIP

A Comprehensive Review of Fetal Tumors with Pathologic Correlation¹

¹ From the Department of Radiologic Pathology, Armed Forces Institute of Pathology, Bldg 54, Rm M-121, 14th and Alaska Ave NW, Washington, DC 20306-6000 (P.J.W.); Oregon Health Science University, Portland, Ore (R.S.); University of Utah, Salt Lake City (A.K.); and Armed Forces Institute of Pathology, Washington, DC (K.K.K.). Received August 5, 2004; revision requested October 6 and received October 19; accepted October 19. All authors have no financial relationships to disclose. Address correspondence to P.J.W. (e-mail: woodwardp@afip.osd.mil).

	Abstract

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
Fetal tumors are a diverse group of neoplasms, which are unique in their histologic characteristics, anatomic distribution, and pathophysiology. The biologic behavior of tumors in the fetus may differ dramatically compared with that of the same tumor detected later in life. Teratomas are the dominant histologic type and constitute the majority of both extracranial and intracranial neoplasms. Although often histologically mature, they may prove lethal because of their location and metabolic demands on the fetus. Large solid tumors may lead to cardiovascular compromise and hydrops fetalis. Extracranial teratomas are most commonly located in the sacrococcygeal area, followed by the head and neck, chest, and retroperitoneum. Fetuses with intracranial tumors have a poor prognosis regardless of histologic type. There are, however, two notable exceptions: lipomas and choroid plexus papillomas, both of which have a more favorable outcome. Neuroblastoma is the most common fetal malignancy. It may be either solid or cystic and is more often located on the right side. It typically has favorable biologic markers and stage at presentation. The prognosis for prenatally diagnosed cases is excellent. Other fetal neoplasms include soft-tissue tumors (both benign and malignant), leukemia, mesenchymal hamartoma of the kidney, and liver tumors (hemangioendothelioma, mesenchymal hamartoma, and hepatoblastoma).

	LEARNING OBJECTIVES FOR TEST 6

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
After reading this article and taking the test, the reader will be able to:

• Describe the histologic types and biologic behavior of fetal tumors.
  
• Delineate those conditions in which prenatal intervention may improve outcome.
  
• Recognize pertinent imaging features, which help differentiate fetal tumors from the more common congenital malformations.
  

	Introduction

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
Fetal tumors, although uncommon, pose a unique circumstance in the care of an obstetric patient and create significant medical and ethical dilemmas. Although the diagnosis of any fetal anomaly is a devastating event for a family, the presence of a fetal tumor carries with it additional diagnostic and therapeutic challenges. The prognosis is generally poor, although there are some notable exceptions. An understanding of the different tumor types and their biologic behavior is necessary for appropriate counseling and care of these patients. Accurate diagnosis has important implications for fetal, maternal, and neonatal care.

The true prevalence of fetal tumors is difficult to determine, as reporting practices vary widely among institutions. Although the reported prevalence for all congenital tumors is in the range of 1.7–13.5 per 100,000 live births, those tumors occurring in fetuses that are stillborn or aborted are most likely underreported in tumor registries (1–4). In addition, the definition of a congenital tumor varies among published series. Clearly, masses in the fetus and newly born infant are congenital. It is also generally agreed that tumors manifesting in the first month of life are also congenital, with some arguing that any tumor developing in the first 3 months of life should be regarded as congenital (1–4).

Controversy also exists about exactly which masses are categorized as congenital tumors. Many series exclude hamartomas, because these lesions contain histologically normal cells derived from the organ of origin. Hemangiomas and lymphangiomas are considered by many to be more appropriately categorized as congenital malformations, rather than true neoplasms. With the exclusion of these three masses, the most common fetal neoplasms are extracranial teratomas, neuroblastomas, soft-tissue tumors, brain tumors, and leukemia (2). Collectively, these tumors constitute approximately 85% of all congenital tumors, with renal tumors, liver tumors, and retinoblastomas constituting the majority of the remainder (4).

To further complicate matters, fetal tumors are truly different from those occurring in childhood; thus, knowledge of tumor type, distribution, and prognosis for tumors occurring in the pediatric population cannot be extrapolated to fetal tumors. Fetal tumors occur with different prevalence, anatomic locations, histologic characteristics, and biologic behavior, compared with pediatric tumors. Some fetal tumors, even though they are histologically benign, may prove fatal because of their size or location. Large benign masses may result in cardiovascular compromise and fetal demise. They may also exert substantial mass effect, inhibiting normal organ development or causing airway obstruction after delivery. The behavior of malignant tumors also cannot be predicted on the basis of known responses in pediatric patients. For example, congenital leukemia has a grim prognosis, whereas neuroblastoma has a more favorable outcome in the fetus and newborn than in older children (4).

The physiology of embryologic development adds to the uniqueness of fetal tumor behavior. No adult tumor grows as rapidly as a normally dividing embryo (4). Normal embryonic cells, with their high mitotic rate, share histologic features with neoplastic cells. One theory of fetal tumor development suggests they do not arise in a previously normally formed organ, as tumors do later in life. They may result from failure of developing tissues to undergo normal cytodifferentiation and maturation. A tumor would be the result of normal immature fetal tissue continuing to divide in an unrestricted fashion (4). Given the mitotic potential of embryonic cells, it is not surprising that fetal tumors (benign as well as malignant) demonstrate remarkable growth rates and reach enormous proportions. It is possible for a large mass to develop within weeks of a normal fetal ultrasound (US) survey (4,5).

Although individual tumors have their own unique characteristics, some features are common to all fetal tumors. Polyhydramnios is the most common, being present in approximately one-third of patients. It may be the first clinical sign, with increased fundal height being noted during an obstetric examination (3). Associated congenital anomalies are present in 20% of cases (particularly with teratomas), and hydrops is reported in 17% (3). If a fetal tumor remains undiagnosed before the onset of labor, the mother may present with dystocia, with the fetus being at significant risk for tumor rupture and exsanguination (4).

Widespread application of screening sonography has increased our awareness of fetal tumors. Doppler sonographic evaluation has advanced our understanding of the pathophysiology of these lesions and the accompanying fetal hemodynamic changes complicating the pregnancy. Magnetic resonance (MR) imaging is ideally suited for evaluation of fetal tumors by virtue of its large field of view and superior soft-tissue contrast. In addition, the rapid evolution of MR imaging technology has yielded fast, and now ultrafast, techniques that provide high-resolution imaging while virtually eliminating motion artifact without fetal sedation (6–13).

Accurate prenatal diagnosis is essential for appropriate planning of both prenatal and postnatal care. These complicated conditions require a multidisciplinary team composed of radiologists, perinatologists, neonatologists, pediatric surgeons, genetic counselors, and social workers. It is essential that we recognize which conditions may be improved with in utero treatment. It is equally important to recognize that our ability to diagnose often exceeds our ability to treat, and that in some cases the best option is to offer supportive care.

In this article, we review the clinical characteristics, imaging appearances, associated abnormalities, natural history, and potential treatments of the varied fetal tumors.

	Teratomas

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
Teratomas form the most common and important group of fetal tumors. Unfortunately, their manifestation in fetal life can be quite dramatic. Teratomas typically occur along the midline of the body, anywhere from the coccyx to the pineal gland. This scattered occurrence is best explained by an aberration in the embryologic development of the gonads (4,14).

Primordial germ cells originate external to the embryo within the yolk sac wall. Between 4 and 6 weeks gestation, they migrate in an amoeba-like fashion along the hindgut and dorsal mesentery to the genital ridges located on either side of the midline. During the migration, primordial germ cells continue to undergo mitosis. Once at the genital ridges, they are incorporated into the primitive sex cords, which form from fingerlike projections of proliferating mesothelium (Fig 1). Together, the primitive sex cords and the primordial germ cells form the primitive gonad, which continues to differentiate into either an ovary or testis (14). During this migratory process, a few of the primordial germ cells may become isolated in an aberrant location. Under normal conditions, germ cells not invested by the sex cords will degenerate and die. Teratomas are thought to arise from unincorporated pluripotential germ cells, which fail to involute and continue to undergo mitosis (4,14).

View larger version (59K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Gonadal embryology. (a) Drawing of a 6-week embryo depicts migration of the primordial germ cells (red dots) from the yolk sac along the hindgut to the genital ridges. (b) Diagram of a midabdominal cross section shows incorporation of the primordial germ cells (red dots) into the primitive sex cords, which will continue to develop into either a testis or ovary. Unincorporated germ cells have the potential to form teratomas.

View larger version (53K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Gonadal embryology. (a) Drawing of a 6-week embryo depicts migration of the primordial germ cells (red dots) from the yolk sac along the hindgut to the genital ridges. (b) Diagram of a midabdominal cross section shows incorporation of the primordial germ cells (red dots) into the primitive sex cords, which will continue to develop into either a testis or ovary. Unincorporated germ cells have the potential to form teratomas.

Teratomas are histologically classified as either mature or immature, with the immature elements consisting principally of primitive neuroglial tissue and neuroepithelial rosettes (Fig 2) (2,3). In a minority of immature teratomas, malignant elements, predominantly yolk sac tumor or embryonal carcinoma, may be present (2). Immature elements are common in fetal teratomas, yet their presence does not carry the same poor prognosis that it does later in life. The immature histologic appearance may be more reflective of the immaturity of the fetus and not necessarily reflective of the biologic behavior of the tumor. The location and size of the mass are far more important than the histologic grade for predicting outcome. Fully resectable, immature teratomas in the newborn have a generally favorable prognosis (4).

View larger version (195K): [in this window] [in a new window] [Download PPT slide]   Figure 2.  Immature teratoma. Photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows ectodermally derived immature neuroglial tissue. Neuroepithelial rosettes (arrows) are seen in a background of cellular stroma.

The initial sign of a fetal sacrococcygeal teratoma may be increased uterine fundal height. Increased uterine size may result from the mass itself or from associated polyhydramnios. Not all patients are symptomatic, with some sacrococcygeal teratomas being discovered during a routine obstetric sonogram. Most sacrococcygeal teratomas are diagnosed in the second trimester, but they have been detected as early as 13.5 weeks gestation (18). Failure to diagnose a fetal sacrococcygeal teratoma during pregnancy can have serious, and potentially catastrophic, consequences for the fetus and the mother. Complications include premature delivery, dystocia, intratumoral hemorrhage, or tumor avulsion with fetal exsanguination (19).

Sacrococcygeal teratomas are classified according to the American Academy of Pediatrics Surgery Section Survey into four types based on the amount of mass present externally versus internally (Fig 3). With type I sacrococcygeal teratoma, the mass is external with minimal or no internal components. Type II is predominantly an external mass with internal extension into the presacral space. Type III is an external and internal mass with extension into the abdominal cavity. Type IV is entirely internal with no external component (20). This system of classification has important prognostic implications in the pediatric population. Pediatric sacrococcygeal teratomas with an undiagnosed internal component are more likely to undergo malignant transformation, and complete resection is required (Fig 4). Malignant transformation of a sacrococcygeal teratoma occurs in 5%–10% of cases diagnosed before 2 months of age and increases to 50%–90% for those diagnosed at 2–4 months of age (15).

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 3a.  Classification of sacrococcygeal teratomas. (a) Type I. Coronal US image of a fetal spine shows a small, exophytic, cystic mass (straight white arrow) emanating from the coccyx (curved arrow). No internal component was identified. Black arrow = iliac crest. (b) Type II. Longitudinal US image of a lower fetal spine shows a mixed cystic and solid sacrococcygeal teratoma (straight arrow), which extends into the presacral space (arrowhead). Curved arrow = coccyx. (c) Type III. Sagittal T2-weighted image shows a mass with a cystic external component and extension of a solid portion into the fetal abdomen (white arrow). Arrowhead = umbilical cord insertion. A type IV mass would have no external component.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 3b.  Classification of sacrococcygeal teratomas. (a) Type I. Coronal US image of a fetal spine shows a small, exophytic, cystic mass (straight white arrow) emanating from the coccyx (curved arrow). No internal component was identified. Black arrow = iliac crest. (b) Type II. Longitudinal US image of a lower fetal spine shows a mixed cystic and solid sacrococcygeal teratoma (straight arrow), which extends into the presacral space (arrowhead). Curved arrow = coccyx. (c) Type III. Sagittal T2-weighted image shows a mass with a cystic external component and extension of a solid portion into the fetal abdomen (white arrow). Arrowhead = umbilical cord insertion. A type IV mass would have no external component.

View larger version (194K): [in this window] [in a new window] [Download PPT slide]   Figure 3c.  Classification of sacrococcygeal teratomas. (a) Type I. Coronal US image of a fetal spine shows a small, exophytic, cystic mass (straight white arrow) emanating from the coccyx (curved arrow). No internal component was identified. Black arrow = iliac crest. (b) Type II. Longitudinal US image of a lower fetal spine shows a mixed cystic and solid sacrococcygeal teratoma (straight arrow), which extends into the presacral space (arrowhead). Curved arrow = coccyx. (c) Type III. Sagittal T2-weighted image shows a mass with a cystic external component and extension of a solid portion into the fetal abdomen (white arrow). Arrowhead = umbilical cord insertion. A type IV mass would have no external component.

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Type II sacrococcygeal teratoma. (a) Clinical photograph of an infant shows an obvious external mass. Preoperative work-up showed that the tumor extended into the presacral space. (b) Intraoperative photograph shows the internal component being resected.

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Type II sacrococcygeal teratoma. (a) Clinical photograph of an infant shows an obvious external mass. Preoperative work-up showed that the tumor extended into the presacral space. (b) Intraoperative photograph shows the internal component being resected.

The sonographic appearance of a sacrococcygeal teratoma is typically that of a heterogeneous, mixed cystic and solid mass. The tumors may be purely cystic in 15% of cases (19). Interrogation with Doppler US is essential to evaluate tumor vascularity. The fetal spine should be meticulously evaluated for defects, as a myelomeningocele is the primary differential diagnosis. In addition, a sacrococcygeal teratoma may involve the spinal canal (6). The diagnosis of intrapelvic extension is important, however, not always possible with US because of poor soft-tissue contrast and shadowing from the pelvic bones. MR imaging has proved to be helpful in better delineating the internal component of a sacrococcygeal teratoma (6,9,13). MR imaging has the further advantage of enabling a truly solid tumor to be differentiated from a diffusely microcystic one, both of which may appear hyperechoic at US (6).

Sacrococcygeal teratomas can grow at a very rapid rate and reach enormous volumes, which can approach and even eclipse the volume of the fetus itself. Size alone, however, is not an independent variable for outcome (21). The most important prognostic indicator is the size of the solid component of the mass. Predominantly cystic tumors, even if large, have a much better prognosis, most likely because they have a lower prevalence of vascular steal and hemorrhage (15,21,22).

Solid tumors can be highly vascular. The metabolic demands of perfusing a large mass, coupled with arteriovenous shunting, can lead to high output cardiac failure and hydrops fetalis (15). Once a sacrococcygeal teratoma has been diagnosed, frequent sonographic surveillance is recommended to look for signs of impending fetal cardiovascular compromise. Evaluation should include measurements of tumor volume, amniotic fluid index, placental thickness, inferior vena cava diameter, and cardiothoracic ratio, as well as Doppler interrogation of the umbilical cord and ductus venosus (Fig 5) (19). If hydrops develops, the prognosis is uniformly poor (16,17,21,23).

View larger version (165K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Sacrococcygeal teratoma with developing cardiovascular failure. (a) US image of a fetal lower spine (Sp) shows a large complex mass with a substantial soft-tissue component (arrows). (b) Color Doppler US image demonstrates prominent feeding vessels (curved arrow) supplying the mass (straight arrow). (c) On a coronal US image of the fetal abdomen, the inferior vena cava (white arrow), compared with the aorta (black arrow, Ao), appears greatly dilated, a finding indicative of impending cardiovascular compromise. (d) Autopsy photograph shows obvious intratumoral hemorrhage within the teratoma.

View larger version (74K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Sacrococcygeal teratoma with developing cardiovascular failure. (a) US image of a fetal lower spine (Sp) shows a large complex mass with a substantial soft-tissue component (arrows). (b) Color Doppler US image demonstrates prominent feeding vessels (curved arrow) supplying the mass (straight arrow). (c) On a coronal US image of the fetal abdomen, the inferior vena cava (white arrow), compared with the aorta (black arrow, Ao), appears greatly dilated, a finding indicative of impending cardiovascular compromise. (d) Autopsy photograph shows obvious intratumoral hemorrhage within the teratoma.

View larger version (163K): [in this window] [in a new window] [Download PPT slide]   Figure 5c.  Sacrococcygeal teratoma with developing cardiovascular failure. (a) US image of a fetal lower spine (Sp) shows a large complex mass with a substantial soft-tissue component (arrows). (b) Color Doppler US image demonstrates prominent feeding vessels (curved arrow) supplying the mass (straight arrow). (c) On a coronal US image of the fetal abdomen, the inferior vena cava (white arrow), compared with the aorta (black arrow, Ao), appears greatly dilated, a finding indicative of impending cardiovascular compromise. (d) Autopsy photograph shows obvious intratumoral hemorrhage within the teratoma.

View larger version (75K): [in this window] [in a new window] [Download PPT slide]   Figure 5d.  Sacrococcygeal teratoma with developing cardiovascular failure. (a) US image of a fetal lower spine (Sp) shows a large complex mass with a substantial soft-tissue component (arrows). (b) Color Doppler US image demonstrates prominent feeding vessels (curved arrow) supplying the mass (straight arrow). (c) On a coronal US image of the fetal abdomen, the inferior vena cava (white arrow), compared with the aorta (black arrow, Ao), appears greatly dilated, a finding indicative of impending cardiovascular compromise. (d) Autopsy photograph shows obvious intratumoral hemorrhage within the teratoma.

The most common associated anomalies seen with sacrococcygeal teratomas are genitourinary and include hydronephrosis, renal dysplasia, urethral atresia, urinary ascites, hydrocolpos, and undescended testes (22,24,25). Other reported anomalies are rectal atresia or stenosis, hip dislocation, and clubbed feet (22). Chromosomal abnormalities are not associated, and amniocentesis is not routinely performed (15).

Clinical management of pregnancies complicated by sacrococcygeal teratoma is often challenging. Significant obstetric complications occurred in 81% of patients in a recent study by Hedrick et al (22). Prenatal complications include polyhydramnios, oligohydramnios, preterm labor, preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and hyperemesis (22). Another reported complication is the mirror syndrome, a potentially life-threatening condition with maternal fluid retention and hemodilution that resembles severe preeclampsia (26). The syndrome occurs in the setting of hydrops fetalis and manifests as progressive maternal edema "mirroring" that of the sick fetus. Immediate delivery is required to reverse this condition (19,21,22,26).

US-guided drainage of primarily cystic sacrococcygeal teratomas may reduce uterine irritability and prevent preterm delivery. It may also be performed immediately before delivery to prevent tumor rupture and to facilitate vaginal birth (Fig 6) (19,22). For solid tumors, there are few prenatal therapeutic options, and delivery should be considered as soon as possible after the lungs are sufficiently mature. Cesarean section is indicated for fetuses with large tumors to avoid dystocia, tumor hemorrhage, and avulsion.

View larger version (73K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  In utero drainage of a large cystic sacrococcygeal teratoma. (a) US image of a cystic sacrococcygeal teratoma shows a needle being inserted into the sac (straight arrow) under US guidance. Curved arrow = tip of the spine. The contents were aspirated, which facilitated vaginal delivery. (b) Photograph of the infant obtained immediately after delivery shows the collapsed sacrococcygeal teratoma (arrow).

View larger version (60K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  In utero drainage of a large cystic sacrococcygeal teratoma. (a) US image of a cystic sacrococcygeal teratoma shows a needle being inserted into the sac (straight arrow) under US guidance. Curved arrow = tip of the spine. The contents were aspirated, which facilitated vaginal delivery. (b) Photograph of the infant obtained immediately after delivery shows the collapsed sacrococcygeal teratoma (arrow).

Head and Neck Teratomas
The head and neck region is the next most common site of teratomas (1,2). Tumors may originate from the thyrocervical area, palate, or nasopharynx and are often large, bulky masses containing both cystic and solid elements. Calcifications are virtually diagnostic of a teratoma, but they are present in only about half of all cases and may not be obvious at US (15).

Cervical teratomas often involve the thyroid gland, although they are not thought to arise directly from thyroid tissue (4). They are unique compared with other teratomas in that there is no female predominance (15). These tumors are frequently large when first diagnosed and may extend posteriorly to the trapezius muscle, superiorly to the mastoid (displacing the ear), and inferiorly to the clavicle or even into the mediastinum (15). They may cause dramatic hyperextension of the fetal neck, resulting in malpresentation and dystocia (Fig 7) (15).

View larger version (166K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Cervical teratoma. (a) Coronal T2-weighted MR image shows a large mixed-signal-intensity mass (curved arrow) within the soft tissues of the fetal neck. The head (straight arrow) is being deviated to the side. (b) Clinical photograph of the infant shows the mass involving the anterior neck with hyperextension of the head.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Cervical teratoma. (a) Coronal T2-weighted MR image shows a large mixed-signal-intensity mass (curved arrow) within the soft tissues of the fetal neck. The head (straight arrow) is being deviated to the side. (b) Clinical photograph of the infant shows the mass involving the anterior neck with hyperextension of the head.

Teratomas associated with the mouth are referred to as epignathi and most commonly arise from the hard or soft palate (4). They typically fill the oral cavity and extend out through the mouth, appearing as an obvious fungating mass that may reach enormous proportions. They often contain both cystic and solid elements with areas of calcification (31) (Fig 8). In cases of epignathi, careful evaluation of the brain is essential, since transphenoidal intracranial extension can occur (4).

View larger version (143K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Epignathus. (a) Coronal US image obtained in the plane of the fetal nose (arrowhead) and lips shows a mass with cystic areas (curved arrow) and calcifications (straight arrow). (b) Three-dimensional reformatted image of the fetal head from an in utero CT examination shows the jaw held in an open position with obvious calcifications within the intraoral portion of the mass. (Reprinted, with permission, from reference 31.)

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Epignathus. (a) Coronal US image obtained in the plane of the fetal nose (arrowhead) and lips shows a mass with cystic areas (curved arrow) and calcifications (straight arrow). (b) Three-dimensional reformatted image of the fetal head from an in utero CT examination shows the jaw held in an open position with obvious calcifications within the intraoral portion of the mass. (Reprinted, with permission, from reference 31.)

Polyhydramnios is a common and important associated finding seen with cervical and oral teratomas and is the result of direct mass effect. Swallowing is compromised by occlusion of the mouth or compression of the esophagus (4,15). It is imperative that these patients be referred to a tertiary care facility for a carefully planned delivery. Reported mortality from lack of airway control is as high as 80%–100% (15,33,34). Even with maximal emergency procedures, hypoxia, acidosis, and anoxic brain injuries may occur.

A substantial improvement in survival can now be achieved by using the ex utero intrapartum treatment (EXIT) procedure (33,35,36). In the EXIT procedure, the fetus is partially delivered by cesarean section while the placenta and umbilical cord remain intact. The uteroplacental gas exchange is maintained, and the fetus remains hemodynamically stable for a considerable amount of time (mean times of 17.7–45 minutes reported) (33,35,36). The EXIT procedure provides a controlled environment in which to accomplish intubation, or if necessary tracheostomy, rather than a "crash" attempt at achieving an airway at birth (Fig 9). Although originallydeveloped for airway management after fetal surgery, the EXIT procedure has been shown to have great usefulness for treating fetuses with obstructing neck masses. Wagner and Harrison (33) reviewed 29 reported cases in which the EXIT procedure was used in the delivery of fetuses with neck masses (tumors and hygromas). An airway was established in 79% of cases, and the overall survival rate was 69%. In another study of 13 fetuses with obstructing neck masses, there was only one death (36). Appropriate planning clearly improves survival in these cases.

View larger version (167K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  EXIT procedure. (a) US image of a fetal profile shows a complex cystic and solid mass (arrow) protruding from the mouth (arrowhead = lower jaw). (b, c) Intraoperative photographs show the intubation. The fetus was delivered via cesarean section and placed on the maternal abdomen. The placenta was left intact, and uteroplacental gas exchange was maintained while intubation was performed. (d) Photograph of the cut gross specimen shows the complex nature of the teratoma.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  EXIT procedure. (a) US image of a fetal profile shows a complex cystic and solid mass (arrow) protruding from the mouth (arrowhead = lower jaw). (b, c) Intraoperative photographs show the intubation. The fetus was delivered via cesarean section and placed on the maternal abdomen. The placenta was left intact, and uteroplacental gas exchange was maintained while intubation was performed. (d) Photograph of the cut gross specimen shows the complex nature of the teratoma.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  EXIT procedure. (a) US image of a fetal profile shows a complex cystic and solid mass (arrow) protruding from the mouth (arrowhead = lower jaw). (b, c) Intraoperative photographs show the intubation. The fetus was delivered via cesarean section and placed on the maternal abdomen. The placenta was left intact, and uteroplacental gas exchange was maintained while intubation was performed. (d) Photograph of the cut gross specimen shows the complex nature of the teratoma.

View larger version (147K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  EXIT procedure. (a) US image of a fetal profile shows a complex cystic and solid mass (arrow) protruding from the mouth (arrowhead = lower jaw). (b, c) Intraoperative photographs show the intubation. The fetus was delivered via cesarean section and placed on the maternal abdomen. The placenta was left intact, and uteroplacental gas exchange was maintained while intubation was performed. (d) Photograph of the cut gross specimen shows the complex nature of the teratoma.

Intrapericardial teratomas are invariably associated with pericardial effusions, which may be massive and mistaken for pleural effusions (Fig 10) (38,39). Large effusions may cause cardiactamponade with resulting cardiovascular compromise and fetal demise. Intrauterine pericardiocentesis has been successfully performed in this setting (39). The primary differential diagnosis is a rhabdomyoma, but they are generally smaller, intracardiac masses, whereas teratomas are external and may be massive.

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Intrapericardial teratoma. (a) Color Doppler US image through a fetal chest shows a large echogenic mass (straight arrow) adjacent to the heart. Note the extensive surrounding pericardial effusion (curved arrows). (b) Coronal T2-weighted image shows a mixed-signal-intensity mass (straight arrow) adjacent to the heart (curved arrow). The mass is surrounded by high-signal-intensity pericardial fluid. No normal lung parenchyma is identified. (c) Autopsy photograph obtained with the pericardium intact shows a massive effusion, with the pericardial sac essentially filling the entire thoracic cavity. (d) Autopsy photograph obtained with the pericardium removed reveals the large teratoma (straight arrow) anterior to the heart (curved arrow).

View larger version (174K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Intrapericardial teratoma. (a) Color Doppler US image through a fetal chest shows a large echogenic mass (straight arrow) adjacent to the heart. Note the extensive surrounding pericardial effusion (curved arrows). (b) Coronal T2-weighted image shows a mixed-signal-intensity mass (straight arrow) adjacent to the heart (curved arrow). The mass is surrounded by high-signal-intensity pericardial fluid. No normal lung parenchyma is identified. (c) Autopsy photograph obtained with the pericardium intact shows a massive effusion, with the pericardial sac essentially filling the entire thoracic cavity. (d) Autopsy photograph obtained with the pericardium removed reveals the large teratoma (straight arrow) anterior to the heart (curved arrow).

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 10c.  Intrapericardial teratoma. (a) Color Doppler US image through a fetal chest shows a large echogenic mass (straight arrow) adjacent to the heart. Note the extensive surrounding pericardial effusion (curved arrows). (b) Coronal T2-weighted image shows a mixed-signal-intensity mass (straight arrow) adjacent to the heart (curved arrow). The mass is surrounded by high-signal-intensity pericardial fluid. No normal lung parenchyma is identified. (c) Autopsy photograph obtained with the pericardium intact shows a massive effusion, with the pericardial sac essentially filling the entire thoracic cavity. (d) Autopsy photograph obtained with the pericardium removed reveals the large teratoma (straight arrow) anterior to the heart (curved arrow).

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 10d.  Intrapericardial teratoma. (a) Color Doppler US image through a fetal chest shows a large echogenic mass (straight arrow) adjacent to the heart. Note the extensive surrounding pericardial effusion (curved arrows). (b) Coronal T2-weighted image shows a mixed-signal-intensity mass (straight arrow) adjacent to the heart (curved arrow). The mass is surrounded by high-signal-intensity pericardial fluid. No normal lung parenchyma is identified. (c) Autopsy photograph obtained with the pericardium intact shows a massive effusion, with the pericardial sac essentially filling the entire thoracic cavity. (d) Autopsy photograph obtained with the pericardium removed reveals the large teratoma (straight arrow) anterior to the heart (curved arrow).

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.  Fetus in fetu. (a) Transverse US image through a fetal abdomen shows a markedly complex mass containing both cystic and solid components and areas of calcification (arrow). (b) Photograph of the gross specimen shows a highly differentiated mass with extremity development. Note the pedicle, which forms the vascular attachment (arrow).

View larger version (72K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.  Fetus in fetu. (a) Transverse US image through a fetal abdomen shows a markedly complex mass containing both cystic and solid components and areas of calcification (arrow). (b) Photograph of the gross specimen shows a highly differentiated mass with extremity development. Note the pedicle, which forms the vascular attachment (arrow).

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.  Fetus in fetu. (a) Axial contrast material-enhanced CT image of an infant shows a large abdominal mass containing fat, fluid, and calcifications resembling vertebrae (arrow). (b) Photograph of the cut surface of the gross specimen shows a well-developed spine, which contained elements of a spinal cord. Other tissues identified were portions of a gastrointestinal tract, cartilage, bone, and bone marrow. All elements were histologically mature.

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.  Fetus in fetu. (a) Axial contrast material-enhanced CT image of an infant shows a large abdominal mass containing fat, fluid, and calcifications resembling vertebrae (arrow). (b) Photograph of the cut surface of the gross specimen shows a well-developed spine, which contained elements of a spinal cord. Other tissues identified were portions of a gastrointestinal tract, cartilage, bone, and bone marrow. All elements were histologically mature.

	Intracranial Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
Primary central nervous system (CNS) tumors are a common group of neoplasms in the pediatric population, being second only to leukemia in frequency (43). The same, however, is not true for the fetus. CNS tumors represent only 10% of all antenatal tumors, ranking behind extracranial teratomas, neuroblastomas, and soft-tissue tumors (43,44).

In addition to relative frequency, other striking differences between fetal and pediatric CNS tumors include histologic characteristics, anatomic location, and prognosis. Intracranial teratoma, a relatively uncommon CNS tumor in children, is the most common fetal brain tumor, accounting for approximately half of all reported cases (5,43,44). They are followed in frequency by astrocytomas of varying grades, lipomas, choroid plexus papillomas, craniopharyngiomas, and primitive neuroectodermal tumors (5,43–45). With regard to anatomic distribution, the majority of fetal CNS tumors are supratentorial, whereas pediatric tumors are more commonly infratentorial (43,44). The third and most clinically significant difference between the two groups is prognosis. Patients with congenital brain tumors have a substantially worse outcome than patients with brain tumors who present later in childhood. The two notable exceptions are fetuses with lipomas and fetuses with choroid plexus papillomas, both of which fare far better than fetuses with other congenital brain tumors (5,45).

The most common prenatal US finding with intracranial tumors is macrocephaly, either as a direct result of the tumor or secondary to associated hydrocephalus. Hydrocephalus usually is caused by direct compressive effects with obstruction of the ventricular system, but it can arise from increased cerebrospinal fluid production from a choroid plexus tumor (43,46). Polyhydramnios, secondary to depressed swallowing from hypothalamic dysfunction, is a common complication. Either hydrocephalus or polyhydramnios may be present before the tumor is sonographically detectable (45).

Congenital brain tumors most commonly arise from the pineal gland, suprasellar area, or cerebral hemispheres; however, the point of origin often cannot be determined with imaging or even autopsy (43). These tumors may exhibit rapid growth over a very short period of time, causing gross distortion of cerebral architecture. The tumors most commonly manifest in the third trimester, sometimes in cases with a normal US scan as recently as 2 weeks prior (5). Associated congenital anomalies are not common (overall frequency, 14% of cases), except for lipomas, which have a strong association with agenesis of the corpus callosum (47,48). The most commonly reported associated malformation is a cleft lip or palate (43).

The imaging appearances of fetal brain tumors overlap considerably. Differentiation of individual tumor types is generally not possible, or even necessary, with imaging. The presence of a large mass disrupts normal neural development and portends a grave outcome, regardless of the histologic characteristics. Teratomas, the most common fetal brain tumors, are generally large, complex, mixed cystic and solid masses with or without foci of calcification (43). They typically arise in the midline, predominantly from the pineal gland, and involve the third ventricle (Fig 13) (45). They may exhibit very rapid growth and reach massive proportions (Fig 14). Most fetuses die in utero or shortly after birth with few long-term survivors (43).

View larger version (143K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  Intracranial teratoma. (a) Transverse US image of a fetal brain shows a predominantly solid, echogenic midline mass (arrow), which is causing obstructive hydrocephalus. (b) Photograph of the gross specimen demonstrates a variegated, lobular mass (straight arrow) with marked thinning of the remaining cerebral tissue (curved arrow).

View larger version (91K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  Intracranial teratoma. (a) Transverse US image of a fetal brain shows a predominantly solid, echogenic midline mass (arrow), which is causing obstructive hydrocephalus. (b) Photograph of the gross specimen demonstrates a variegated, lobular mass (straight arrow) with marked thinning of the remaining cerebral tissue (curved arrow).

View larger version (92K): [in this window] [in a new window] [Download PPT slide]   Figure 14a.  Intracranial teratoma. (a) Transverse US image of a fetal brain shows a large, heterogeneous mass within the cranial vault (cursors) completely destroying normal anatomic landmarks. Measurements showed marked macrocephaly. (b) Postmortem coronal T1-weighted image demonstrates complete replacement of brain tissue by a complex mixed-signal-intensity mass. Immature teratoma (with primitive neural tissue, cartilage, bone, intestinal mucosa, smooth muscle, and hemorrhage) was identified at autopsy.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 14b.  Intracranial teratoma. (a) Transverse US image of a fetal brain shows a large, heterogeneous mass within the cranial vault (cursors) completely destroying normal anatomic landmarks. Measurements showed marked macrocephaly. (b) Postmortem coronal T1-weighted image demonstrates complete replacement of brain tissue by a complex mixed-signal-intensity mass. Immature teratoma (with primitive neural tissue, cartilage, bone, intestinal mucosa, smooth muscle, and hemorrhage) was identified at autopsy.

Two other less common tumors, which may occur as large cerebral masses, are craniopharyngioma and primitive neuroectodermal tumor (PNET). Craniopharyngiomas arise from the Rathke pouch, an ectodermal diverticulum from the roof of the mouth, and form a suprasellar mass. They are heterogeneous, complex masses, which frequently calcify and are indistinguishable from teratomas at prenatal imaging (44). Primitive neuroectodermal tumors are a group of highly malignant, small cell tumors thought to derive from the neural crest (43). Although primitive neuroectodermal tumors are relatively common in the first year of life, they constitute only 3.4%–13.2% of fetal CNS tumors (43,45,48).

Choroid plexus papillomas are comparatively more common in fetuses than in children, accounting for approximately 5%–9% of congenital brain tumors in contrast to 1.6% of pediatric brain tumors (43,45,48). The most common site of occurrence is the lateral ventricle, but they can form anywhere there is choroid in the ventricular system. Rapid onset of hydrocephalus may occur from increased production of cerebrospinal fluid. On US images, choroid plexus papillomas are well-defined, lobular, hyperechoic, intraventricular masses (Figs 15, 16). They should not be confused with the much more common choroid plexus cyst.

View larger version (142K): [in this window] [in a new window] [Download PPT slide]   Figure 15a.  Choroid plexus papilloma. (a, b) Transverse (a) and parasagittal (b) US images of a fetal head show a well-defined, lobular, hyperechoic mass (arrow) within the atrium of the right lateral ventricle. Hydrocephalus is also present. (c) Axial contrast-enhanced CT image of the brain demonstrates substantial enhancement of the mass (arrow). There is severe hydrocephalus with transependymal edema (arrowheads). (d) Photograph of the resected tumor shows the characteristic lobular contour.

View larger version (143K): [in this window] [in a new window] [Download PPT slide]   Figure 15b.  Choroid plexus papilloma. (a, b) Transverse (a) and parasagittal (b) US images of a fetal head show a well-defined, lobular, hyperechoic mass (arrow) within the atrium of the right lateral ventricle. Hydrocephalus is also present. (c) Axial contrast-enhanced CT image of the brain demonstrates substantial enhancement of the mass (arrow). There is severe hydrocephalus with transependymal edema (arrowheads). (d) Photograph of the resected tumor shows the characteristic lobular contour.

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 15c.  Choroid plexus papilloma. (a, b) Transverse (a) and parasagittal (b) US images of a fetal head show a well-defined, lobular, hyperechoic mass (arrow) within the atrium of the right lateral ventricle. Hydrocephalus is also present. (c) Axial contrast-enhanced CT image of the brain demonstrates substantial enhancement of the mass (arrow). There is severe hydrocephalus with transependymal edema (arrowheads). (d) Photograph of the resected tumor shows the characteristic lobular contour.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 15d.  Choroid plexus papilloma. (a, b) Transverse (a) and parasagittal (b) US images of a fetal head show a well-defined, lobular, hyperechoic mass (arrow) within the atrium of the right lateral ventricle. Hydrocephalus is also present. (c) Axial contrast-enhanced CT image of the brain demonstrates substantial enhancement of the mass (arrow). There is severe hydrocephalus with transependymal edema (arrowheads). (d) Photograph of the resected tumor shows the characteristic lobular contour.

View larger version (169K): [in this window] [in a new window] [Download PPT slide]   Figure 16a.  Choroid plexus papilloma. (a) Axial US image of a fetal brain shows an echogenic mass filling and expanding the third ventricle (arrow). There is severe hydrocephalus with dangling choroid plexuses (arrowheads). (b) Coronal US image of the brain obtained after delivery demonstrates that the mass is within the third ventricle (arrow).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 16b.  Choroid plexus papilloma. (a) Axial US image of a fetal brain shows an echogenic mass filling and expanding the third ventricle (arrow). There is severe hydrocephalus with dangling choroid plexuses (arrowheads). (b) Coronal US image of the brain obtained after delivery demonstrates that the mass is within the third ventricle (arrow).

Lipoma, a benign fatty tumor, has the best prognosis of all the intracranial tumors. The prevalence of intracranial lipomas is underestimated in pathologic series because they are often asymptomatic and not generally resected. In two reviews that specifically analyzed brain tumors diagnosed with prenatal US, lipomas represented approximately 10% of cases (5,45). On US images, they are well-defined, hyperechoic masses either in the midline or associated with the lateral ventricles (Fig 17). With an average diameter of 1.6 cm, they are the smallest of the intracranial tumors and are generally not diagnosed until the middle to late third trimester (45). Lipomas in the midline are frequently associated with agenesis of the corpus callosum. MR imaging is particularly helpful in these cases to confirm fat within the mass and to look for agenesis of the corpus callosum, which can be difficult to diagnose with US (5,10,12).

View larger version (152K): [in this window] [in a new window] [Download PPT slide]   Figure 17a.  Lipoma with agenesis of the corpus callosum. (a) Coronal US image of a fetal head shows a midline, echogenic mass in the region of the corpus callosum (arrow). This appearance is characteristic of a lipoma, and the rest of the brain should be carefully evaluated for agenesis of the corpus callosum. (b) Photograph of the brain (infant died of other causes) demonstrates a lipoma (arrow), which corresponds to the mass seen at US. Note absence of the corpus callosum, which would normally be seen as a band of tissue connecting the two cerebral hemispheres.

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 17b.  Lipoma with agenesis of the corpus callosum. (a) Coronal US image of a fetal head shows a midline, echogenic mass in the region of the corpus callosum (arrow). This appearance is characteristic of a lipoma, and the rest of the brain should be carefully evaluated for agenesis of the corpus callosum. (b) Photograph of the brain (infant died of other causes) demonstrates a lipoma (arrow), which corresponds to the mass seen at US. Note absence of the corpus callosum, which would normally be seen as a band of tissue connecting the two cerebral hemispheres.

The overall prognosis for fetal brain tumors, except for lipomas and choroid plexus papillomas, is dismal. Low-grade astrocytomas and gangliogliomas have a slightly better prognosis, whereas teratomas, primitive neuroectodermal tumors, craniopharyngiomas, and glioblastomas are almost uniformly fatal (5,43–45). Diagnosis earlier in pregnancy, particularly before 30 weeks gestation, portends a particularly grave prognosis, with mortality rates as high as 96.9% reported (45). Cavalheiro et al (51) suggest that the poor outcome may be more related to the affects of hydrocephalus than the tumor itself. They report performing repeated cephalocentesis on five fetuses to decompress hydrocephalus, which resulted in improved survival.

Given the grim prognosis, termination of pregnancy may be considered, or in those cases presenting late, treatment may be strictly supportive. Cephalocentesis before the onset of labor may be considered to allow for a vaginal delivery, or cesarean section may be required to prevent dystocia. Because these tumors are usually large and associated with neural destruction, surgical resection is often not possible. Unresectable tumors may be treated with chemotherapy, but irradiation is generally contraindicated because of side effects on normal brain growth and development (5,44). Despite technologic and surgical advances, survivors are often left with substantial psychomotor deficits.

Neuroblastomas
Neuroblastoma is the most common congenital malignancy. It accounts for approximately 30% of all fetal tumors and is second only to extracranial teratomas in overall frequency (52). Neuroblastoma is derived from primordial neural crest cells that form the sympathetic ganglion and, as a result, may occur anywhere along that chain (53). Greater than 90% of fetal cases occur in the adrenal gland, compared with only 35% being of adrenal origin in the pediatric population (52,53).

Although neuroblastoma in the fetus has been reported as early as 20 weeks gestation, most fetal neuroblastomas are diagnosed after 32 weeks. They are typically suprarenal and right sided (54,55). Approximately half of all these tumors are cystic, although they may appear as solid or complex masses at US (Figs 18, 19) (52,55–57). Calcifications, a common feature in pediatric neuroblastoma, are less often reported in fetal neuroblastoma.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 18a.  Neuroblastoma. (a) Coronal US image of a fetal body shows a well-defined echogenic mass (cursors) above the right kidney (RK). (b) Longitudinal US image obtained after delivery demonstrates the solid suprarenal mass (cursors). (c) Photograph of the resected tumor and right kidney. The tumor was confined to the adrenal gland. (Reprinted, with permission, from reference 53.)

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 18b.  Neuroblastoma. (a) Coronal US image of a fetal body shows a well-defined echogenic mass (cursors) above the right kidney (RK). (b) Longitudinal US image obtained after delivery demonstrates the solid suprarenal mass (cursors). (c) Photograph of the resected tumor and right kidney. The tumor was confined to the adrenal gland. (Reprinted, with permission, from reference 53.)

View larger version (90K): [in this window] [in a new window] [Download PPT slide]   Figure 18c.  Neuroblastoma. (a) Coronal US image of a fetal body shows a well-defined echogenic mass (cursors) above the right kidney (RK). (b) Longitudinal US image obtained after delivery demonstrates the solid suprarenal mass (cursors). (c) Photograph of the resected tumor and right kidney. The tumor was confined to the adrenal gland. (Reprinted, with permission, from reference 53.)

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 19.  Cystic neuroblastoma. Longitudinal US image of a fetal abdomen shows a large, complex cystic mass (straight arrow) above the right kidney (RK).

During embryologic development, the fetal adrenal gland normally contains neuroblastic nodules, which are histologically indistinguishable from neuroblastoma in situ. The number of neuroblastic nodules peaks at 17–20 weeks gestation, and they subsequently mature or regress (15,53,59). The nodules are found in 100% of second-trimester abortuses and in 0.5%–2.5% of neonates dying from other causes (15). Therefore, the presence of "neuroblastoma in situ" in autopsy series is significantly higher than the clinical prevalence of the disease, which is one in 10,000–30,000 (15). It may be that sonographically detectable fetal lesions represent a temporary defect in the growth of these nodules that may involute with time (59).

Data from infant screening programs support the theory that many localized adrenal masses are likely to mature or regress without becoming clinically evident. These programs have resulted in a marked increase in the detection of stage I tumors, with no change in the prevalence of tumors detected in older children (when the prognosis is worse) or impact on overall survival rates (15,53,58,60). It is likely that many of the incidentally encountered fetal tumors would, likewise, never have become clinically apparent (52,58).

It is also interesting to note the predominance of cystic neuroblastoma in fetuses. Cystic changes may indicate ongoing involution. At histologic analysis, these tumors have small aggregates of neuroblasts in the cyst wall, rather than sheets of tumor cells (52). Cystic tumors usually have favorable biologic markers and are less likely to be chemically active (52,56).

Tumor stage at presentation is an important prognostic factor, and the neuroblastomas most commonly occurring in fetuses are in more favorable categories (ie, stages I, II, and IVS). In stage I disease, the tumor is confined to the adrenal gland. Stage II tumors demonstrate local extension beyond the adrenal gland without crossing the midline. Stage IVS is a unique grouping of metastases including those to the liver, skin, and <10% of bone marrow (not bone). Acharya et al (52) reviewed 55 prenatally diagnosed cases in which 93% had a favorable stage: the majority (67%) were stage I, with 4% in stage II and 22% in stage IVS.

In addition to stage, there are some specific biologic markers that influence the generally favorable course of neuroblastomas in fetuses. Myc-N is a proto-oncogene, which portends rapid tumor progression when it is present in multiple copies (Myc-N amplification) (53). The deoxyribonucleic acid (DNA) content of the tumor cells is also a prognostic indicator. Tumor cells with a diploid DNA content (DNA index of 1) are biologically aggressive, whereas tumor cells with increased DNA content (DNA index greater than 1) have a more favorable prognosis (53). Most fetal neuroblastomas have a favorable DNA index (>1) and no Myc-N amplification (52).

Although most fetal neuroblastomas are stage I, they do not always remain localized to the adrenal gland, with solid tumors being more likely to metastasize. The liver is the most common site for metastases and is involved in 25% of fetal cases (stage IV or IVS) (Fig 20) (52). Two metastatic patterns occur: diffuse infiltration (more common in stage IVS disease) and focal masses (53). The diffuse form may be difficult to diagnose prenatally but should be suspected when hepatomegaly or hydrops is present (52). Fetal MR imaging may prove to be helpful, but normal findings do not completely exclude involvement (54). In rare cases, neuroblastoma may metastasize to the chorionic villi of the placenta, but no cases of maternal metastases have been documented (59).

View larger version (184K): [in this window] [in a new window] [Download PPT slide]   Figure 20a.  Stage IV neuroblastoma. (a) Transverse US image of a fetal abdomen shows a large, solid adrenal mass (curved arrow). The liver is heterogeneous with several discrete metastases (arrowheads). Ascites is also present (straight arrow). (b, c) Autopsy photographs show the large solid mass above the kidney (b) and diffuse liver metastases (c). Metastases were also present in the bone and placenta.

View larger version (70K): [in this window] [in a new window] [Download PPT slide]   Figure 20b.  Stage IV neuroblastoma. (a) Transverse US image of a fetal abdomen shows a large, solid adrenal mass (curved arrow). The liver is heterogeneous with several discrete metastases (arrowheads). Ascites is also present (straight arrow). (b, c) Autopsy photographs show the large solid mass above the kidney (b) and diffuse liver metastases (c). Metastases were also present in the bone and placenta.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 20c.  Stage IV neuroblastoma. (a) Transverse US image of a fetal abdomen shows a large, solid adrenal mass (curved arrow). The liver is heterogeneous with several discrete metastases (arrowheads). Ascites is also present (straight arrow). (b, c) Autopsy photographs show the large solid mass above the kidney (b) and diffuse liver metastases (c). Metastases were also present in the bone and placenta.

Only half of all suprarenal masses are neuroblastomas, so it is important to evaluate a suprarenal mass carefully before arriving at this diagnosis (57). For a solid suprarenal mass, the primary differential diagnosis is an extralobar sequestration. An extralobar sequestration usually occurs on the left (60% of neuroblastomas are right-sided) and is seen earlier (second trimester) than neuroblastoma (54). Color Doppler US may depict a dominant feeding vessel from the aorta that supplies the sequestration (54). Adrenal hemorrhage can also resemble a neuroblastoma. It is commonly seen in neonates but is rarer in a fetus, although adrenal hemorrhage has been reported in third-trimester fetuses (57,61). A duplicated renal collecting system or focal multicystic dysplastic kidney may be confused for a cystic neuroblastoma.

Surgery remains the standard treatment and is curative in most cases. However, because of the indolent course of many of the incidentally noted neuroblastomas, some advocate a more conservative approach of close surveillance rather than immediate surgery. Acharya et al (52) recommend monthly sonograms for 6 months for infants whose tumors were detected in utero, especially if the tumors are small (<3 cm) and cystic. Solid lesions require biopsy, and those with poor biologic features, liver metastases, or failure to involute need surgical resection.

	Soft-tissue Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
The soft tissues give rise to an exceedingly diverse group of tumors. Although relatively common in pathologic series, representing 12%–22% of all congenital tumors, soft-tissue tumors are much less commonly reported in the radiology literature (62). This discrepancy is likely because of both tumor size and location. Masses may be small and located in the soft tissues of the extremities, an area that often does not receive the same careful scrutiny as fetal organs. In addition, soft-tissue tumors are less likely to cause in utero complications such as polyhydramnios and hydrops. The majority of congenital soft-tissue tumors manifest in the newborn period as a palpable mass. Approximately two-thirds of these tumors are benign; however, they can be locally aggressive, often requiring wide excisions (62).

Fibrous connective tissue tumors form the largest group of congenital soft-tissue tumors. These tumors include fibromatosis, myofibromatosis, digital fibromatosis, fibrous hamartoma, and infantile fibrosarcoma, with the latter being the most common soft-tissue malignancy in newborns (62,63). Fibrosarcoma generally occurs in the extremities, but it has also been reported in the back, neck, and retroperitoneum (Fig 21) (62,64,65). Fibrosarcoma tends to be less aggressive than other soft-tissue sarcomas and has a low metastatic rate (60).

View larger version (175K): [in this window] [in a new window] [Download PPT slide]   Figure 21a.  Fibrosarcoma. (a) US image of the upper legs of a fetus shows dramatic thickening of the soft tissues around the distal left thigh and knee (arrow). (b) Gross photograph shows the left leg soft-tissue mass. (Reprinted, with permission, from reference 64.)

View larger version (91K): [in this window] [in a new window] [Download PPT slide]   Figure 21b.  Fibrosarcoma. (a) US image of the upper legs of a fetus shows dramatic thickening of the soft tissues around the distal left thigh and knee (arrow). (b) Gross photograph shows the left leg soft-tissue mass. (Reprinted, with permission, from reference 64.)

View larger version (170K): [in this window] [in a new window] [Download PPT slide]   Figure 22.  Rhabdosarcoma. Axial T2-weighted image obtained through the level of the fetal orbits shows a fungating soft-tissue mass (straight arrow) emanating from the left orbit. The right eye (curved arrow) is normal.

View larger version (155K): [in this window] [in a new window] [Download PPT slide]   Figure 23a.  Hemangiopericytoma. (a) Transverse US image of a fetal chest shows asymmetric thickening of the lateral chest wall (arrow). (b) Axial unenhanced CT image, obtained with a metallic marker over the area of palpable abnormality, demonstrates increased soft tissue compared with the opposite side. (c) Intraoperative photograph obtained during excision shows the lobular mass. Histologic findings confirmed the diagnosis of hemangiopericytoma.

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 23b.  Hemangiopericytoma. (a) Transverse US image of a fetal chest shows asymmetric thickening of the lateral chest wall (arrow). (b) Axial unenhanced CT image, obtained with a metallic marker over the area of palpable abnormality, demonstrates increased soft tissue compared with the opposite side. (c) Intraoperative photograph obtained during excision shows the lobular mass. Histologic findings confirmed the diagnosis of hemangiopericytoma.

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 23c.  Hemangiopericytoma. (a) Transverse US image of a fetal chest shows asymmetric thickening of the lateral chest wall (arrow). (b) Axial unenhanced CT image, obtained with a metallic marker over the area of palpable abnormality, demonstrates increased soft tissue compared with the opposite side. (c) Intraoperative photograph obtained during excision shows the lobular mass. Histologic findings confirmed the diagnosis of hemangiopericytoma.

	Renal Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 24a.  Mesoblastic nephroma. (a) Oblique coronal US image of a fetal kidney shows a markedly enlarged lower pole, which is extending into the pelvis and abutting the bladder (B). The upper pole has a normal appearance (white arrows), whereas the lower pole is replaced by a large solid mass (black arrows). (b) Photograph of the resected kidney shows a well-defined, fleshy, lower pole mass with a dense stromal architecture. Scale is in centimeters.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 24b.  Mesoblastic nephroma. (a) Oblique coronal US image of a fetal kidney shows a markedly enlarged lower pole, which is extending into the pelvis and abutting the bladder (B). The upper pole has a normal appearance (white arrows), whereas the lower pole is replaced by a large solid mass (black arrows). (b) Photograph of the resected kidney shows a well-defined, fleshy, lower pole mass with a dense stromal architecture. Scale is in centimeters.

View larger version (134K): [in this window] [in a new window] [Download PPT slide]   Figure 25a.  Mesoblastic nephroma. (a) Axial US image through a fetal abdomen is most striking for associated severe polyhydramnios. There is a large solid mass in the region of the right kidney (straight arrow). The left kidney is normal (curved arrow). (b) Axial contrast-enhanced CT scan obtained after delivery shows dramatic enlargement of the right kidney with essentially complete replacement by the tumor.

View larger version (92K): [in this window] [in a new window] [Download PPT slide]   Figure 25b.  Mesoblastic nephroma. (a) Axial US image through a fetal abdomen is most striking for associated severe polyhydramnios. There is a large solid mass in the region of the right kidney (straight arrow). The left kidney is normal (curved arrow). (b) Axial contrast-enhanced CT scan obtained after delivery shows dramatic enlargement of the right kidney with essentially complete replacement by the tumor.

Neonates typically have an obvious palpable mass on examination. Other findings may include hypertension (secondary to increased renin production) and hypercalcemia (67). Both calcium and renin levels return to normal after resection. This tumor has an excellent prognosis, with nephrectomy being curative in most cases.

	Liver Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
The liver is embryologically derived from both mesenchymal and endodermal tissues and thus can develop a wide variety of both benign and malignant neoplasms. Collectively, liver masses represent approximately 5% of all congenital tumors (70). The lesions most commonly seen in the perinatal period include hemangioendothelioma, mesenchymal hamartoma, hepatoblastoma, and metastases (particularly those from neuroblastoma and leukemia) (70).

The histogenesis of benign vascular liver tumors is not completely clear, which has led to some confusion in terminology. In the literature, vascular tumors are variably described as hemangioma, infantile hemangioma, hepatic arteriovenous malformation, and infantile hemangioendothelioma. Infantile hemangioendothelioma describes a lesion composed of large endothelial-lined vascular channels (the type more commonly seen in fetuses and neonates), which is histologically distinct from hemangioma (71). Both hemangioma and infantile hemangioendothelioma may occur concurrently. In 10%–15% of cases of hemangioendothelioma of the liver, hemangiomas may also be present in other organs, including the skin (71).

Hemangioendotheliomas have been detected in utero as early as 16 weeks gestation (72). These tumors have a variable sonographic appearance and may be either hypoechoic or hyperechoic or may have mixed echogenicity. Color Doppler US evaluation will show increased flow, and a flow void in the mass has been observed with fetal MR imaging (72–74). Substantial arteriovenous shunting may lead to fetal cardiovascular compromise and hydrops. In addition, fetuses may also develop hemolytic anemia, thrombocytopenia, and consumptive coagulopathy, the so-called Kasabach-Merritt sequence (70). If these tumors are not detected prenatally, neonates may present with unexplained congestive heart failure (Fig 26) (75).

View larger version (176K): [in this window] [in a new window] [Download PPT slide]   Figure 26a.  Hemangioendothelioma. (a) Transverse US image through a fetal abdomen shows a large, irregular, heterogeneous mass (arrows) essentially replacing the liver. (b) Frontal radiograph of the chest and abdomen obtained after delivery shows obvious congestive heart failure with cardiac enlargement and soft-tissue edema. Also note the fullness in the right upper quadrant and displacement of bowel loops by the liver mass. (c) Autopsy photograph of the liver demonstrates the large, irregular mass with areas of fibrosis and hemorrhage. (d) Photograph of the foot shows a coexistent cutaneous hemangioma.

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 26b.  Hemangioendothelioma. (a) Transverse US image through a fetal abdomen shows a large, irregular, heterogeneous mass (arrows) essentially replacing the liver. (b) Frontal radiograph of the chest and abdomen obtained after delivery shows obvious congestive heart failure with cardiac enlargement and soft-tissue edema. Also note the fullness in the right upper quadrant and displacement of bowel loops by the liver mass. (c) Autopsy photograph of the liver demonstrates the large, irregular mass with areas of fibrosis and hemorrhage. (d) Photograph of the foot shows a coexistent cutaneous hemangioma.

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 26c.  Hemangioendothelioma. (a) Transverse US image through a fetal abdomen shows a large, irregular, heterogeneous mass (arrows) essentially replacing the liver. (b) Frontal radiograph of the chest and abdomen obtained after delivery shows obvious congestive heart failure with cardiac enlargement and soft-tissue edema. Also note the fullness in the right upper quadrant and displacement of bowel loops by the liver mass. (c) Autopsy photograph of the liver demonstrates the large, irregular mass with areas of fibrosis and hemorrhage. (d) Photograph of the foot shows a coexistent cutaneous hemangioma.

View larger version (91K): [in this window] [in a new window] [Download PPT slide]   Figure 26d.  Hemangioendothelioma. (a) Transverse US image through a fetal abdomen shows a large, irregular, heterogeneous mass (arrows) essentially replacing the liver. (b) Frontal radiograph of the chest and abdomen obtained after delivery shows obvious congestive heart failure with cardiac enlargement and soft-tissue edema. Also note the fullness in the right upper quadrant and displacement of bowel loops by the liver mass. (c) Autopsy photograph of the liver demonstrates the large, irregular mass with areas of fibrosis and hemorrhage. (d) Photograph of the foot shows a coexistent cutaneous hemangioma.

A mesenchymal hamartoma is a benign liver tumor composed of large, fluid-filled cysts surrounded by loose mesenchymal tissue containing small bile ducts (71). This tumor appears as a predominantly cystic or mixed echogenicity mass and should be a primary consideration in the differential diagnosis of an enlarging cystic liver lesion (Fig 27). Although the gray-scale US appearance of mesenchymal hamartoma overlaps substantially with that of hemangioendothelioma, the former masses do not have increased vascularity at color Doppler US (76,77). Hydrops may develop, not from vascular shunting, but from a rapid shift of body fluid into the cyst (77). Surgery is curative but not always possible if the mass extensive.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 27a.  Mesenchymal hamartoma. (a) Transverse US image of a fetal abdomen shows a predominantly cystic mass associated with the liver (arrow). (b) Photograph of the resected specimen demonstrates the typical large cystic spaces in a background of disorganized mesenchymal tissue.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 27b.  Mesenchymal hamartoma. (a) Transverse US image of a fetal abdomen shows a predominantly cystic mass associated with the liver (arrow). (b) Photograph of the resected specimen demonstrates the typical large cystic spaces in a background of disorganized mesenchymal tissue.

View larger version (173K): [in this window] [in a new window] [Download PPT slide]   Figure 28a.  Hepatoblastoma. (a) Transverse US image obtained at the level of the fetal liver shows a large, well-demarcated solid mass (arrow). Note the areas of alternating echogenicity, giving the mass a "spoked-wheel" appearance. (b) Autopsy photograph of the liver shows the well-defined mass with prominent fibrous bands extending to the pseudocapsule.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 28b.  Hepatoblastoma. (a) Transverse US image obtained at the level of the fetal liver shows a large, well-demarcated solid mass (arrow). Note the areas of alternating echogenicity, giving the mass a "spoked-wheel" appearance. (b) Autopsy photograph of the liver shows the well-defined mass with prominent fibrous bands extending to the pseudocapsule.

	Leukemia

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 29a.  Congenital leukemia. (a) Longitudinal US image of a fetus (spine up) shows a massively enlarged liver causing a protuberant abdomen (arrows). Compare the abdomen to the size of the chest (arrowhead). (b) Autopsy photograph shows hepatomegaly. The spleen was also enlarged.

View larger version (134K): [in this window] [in a new window] [Download PPT slide]   Figure 29b.  Congenital leukemia. (a) Longitudinal US image of a fetus (spine up) shows a massively enlarged liver causing a protuberant abdomen (arrows). Compare the abdomen to the size of the chest (arrowhead). (b) Autopsy photograph shows hepatomegaly. The spleen was also enlarged.

The primary differential diagnosis for unexplained hepatosplenomegaly and nonimmune hydrops is infection. Metastatic neuroblastoma may also have a similar appearance. When congenital leukemia is suspected, cordocentesis is performed; the diagnosis of fetal leukemia is made based on the results of white blood cell analysis. Given the strong association of congenital leukemia with Down syndrome, karyotyping should always be performed.

	Conclusions

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 
Congenital tumors represent a diverse group of benign and malignant masses that often have a devastating effect on the fetus and the pregnancy. Although congenital tumors are rare, we expect that with the ever-increasing use of US in routine obstetric screening, the number of cases detected prenatally will increase. Many of these tumors achieve great size, and their appearance at prenatal imaging is confusing and bizarre. Because of their location or vascularity, they may manifest with secondary problems such as hydrops fetalis and polyhydramnios. It is imperative for the diagnostic physician to be familiar with fetal tumors to not mistake them for other more common anomalies. In addition, each tumor is unique in its natural history, histologic characteristics, anatomic location, and prognosis. A thorough understanding of all these features is necessary to assemble the appropriate multidisciplinary team and to guide patient care.

	Footnotes

 
Abbreviation: CNS = central nervous system

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as representing the views of the Departments of the Navy or Defense.

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Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Teratomas Intracranial Tumors Soft-tissue Tumors Renal Tumors Liver Tumors Leukemia Conclusions References

 

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