Tumors of the liver are rare during the perinatal period. They account for only 5% of all neoplasms that occur in the fetus and the newborn (Campbell et al., 1987; Borch et al., 1992; Broadbent, 1992; Werbe et al., 1992; Isaacs, 1997). The most common primary hepatic tumor is hemangioma, followed by mesenchymal hamartoma and hepatoblastoma (Stocker and Ishak, 1983; Isaacs, 1985; Davis et al., 1988; Davenport et al., 1995; von Schweinitz, 2003; Laberge et al., 2005; Christison-Lagay et al., 2007; Isaacs, 2007). Each has been detected prenatally by ultrasound examination and can be detected postnatally by palpation of an abdominal mass (Romero et al., 1988; Garmel et al., 1994; Isaacs, 1997; Isaacs, 2007). However, metastatic lesions are more common than primary liver tumors (Dehner, 1978; Coffin and Dehner, 1992). The most common tumor that metastasizes to the liver in the fetus and newborn is neuroblastoma, followed by leukemia, yolk sac tumor from sacrococcygeal teratoma, and rhabdoid tumor of the kidney (Dehner, 1978; Isaacs, 1985, Isaacs, 1997). The majority of hepatic hemangiomas are diagnosed before the age of 6 months and almost 50% appear within the first week of life (Dehner et al., 1975; Laird et al., 1976; Stanley et al., 1977, Dehner, 1978, Dehner, 1981, Ehren et al., 1983; Miller and Greenspan, 1985a and Miller and Greenspan, 1985b; Golitz et al., 1986; Dehner, 1987; Davis et al., 1988; Luks et al., 1991; Drut et al., 1992; Werbe et al., 1992). There have been multiple reports in the literature of hepatic hemangiomas diagnosed by prenatal sonographic examination (Nakamoto et al., 1983; Platt et al., 1983; Horgan et al., 1984; Petrovic et al., 1992; Sepulveda et al., 1993; Chou et al., 2005; Isaacs, 2007). In the report by Isaacs, reviewing reported cases in the literature and experience at Children’s Hospital San Diego and Children’s Hospital Los Angeles, he found that of the 194 fetal and neonatal tumors, 29% presented antenatally (Isaacs, 2007). The most common of these were hepatic hemangiomas, accounting for 117 of the 194 tumors, with 28% presenting antenatally. The most common antenatal presentation was the sonographic detection of a hepatic mass followed by anemia, hydrops, polyhydramnios, heart failure, thrombocytopenia, and disseminated intravascular coagulation (Isaacs, 2007). It is likely that more hemangiomas occur in the liver than are actually recognized, because many are asymptomatic or silent conditions that regress or are discovered as only an incidental finding on clinical imaging or postmortem examination (Dehner, 1978). Some hemangiomas, in contrast, present with hepatomegaly or a mass lesion and high-output cardiac failure, while others may be life-threatening during the perinatal period because of rupture of the hemangioma and hemoperitoneum during delivery (Dehner, 1981; Larcher et al., 1981; Miller and Greenspan, 1985a and Miller and Greenspan, 1985b; Weinberg and Finegold, 1986; Dehner, 1987; Romero et al., 1988; Stanley et al., 1989; Berry, 1993; Davenport et al., 1995). Hemangiomas have been associated with consumptive coagulopathy resulting from disseminated intravascular coagulation (DIC), sequestration of platelets causing a bleeding diathesis (Kasabach–Merritt syndrome), and anemia (Dehner, 1987; Slopeck and Lakatau, 1989; Isaacs, 1991; Berry, 1993; Isaacs, 2007). High-output cardiac failure leading to in utero demise as a result of hepatic hemangioma has been described by (Nakamoto et al. (1983); Isaacs, 2007). In a report from Stanley et al. (1989) a palpable abdominal mass and cardiac failure were the most frequent presenting findings in 20 infants diagnosed with hepatic hemangiomas. Hepatic hemangiomas can be focal or multifocal. Most focal hemangiomas occur in the right lobe of the liver (Isaacs, 2007). Associated extrahepatic hemangiomas most often occur in skin, brain, placenta, lungs, and eyes. In about 50% of newborns, hepatic hemangiomas are associated with hemangiomas of the skin and other organs (Dehner, 1978; Shturman-Ellstein et al., 1978; Larcher et al., 1981; Isaacs, 1985; Golitz et al., 1986; Dehner, 1987; Stanley et al., 1989; Berry, 1993; Leonidas et al., 1993; Davenport et al., 1995; Isaacs, 2007). The fatal combination of cutaneous and hepatic hemangiomas, hydrops fetalis, hydramnios, and premature delivery has been reported by Shturman-Ellstein et al. (1978). This case was also notable for associated placental edema and chorioangioma, with a terminal clinical course complicated by thrombocytopenia and DIC in the Kasabach–Merritt syndrome that was further compromised by respiratory distress syndrome (Shturman-Ellstein et al., 1978).

Congenital malformations may also be observed in association with hepatic hemangiomas. Werbe et al. (1992) described two such cases in stillborn infants. One infant had a 4-cm hemangioma and an encephalocele, while the other had two liver lesions in addition to encephalomyelitis, partial gut malrotation, and single umbilical artery. In another report, congenital heart disease and prune belly syndrome, respectively, occurred with hepatic hemangiomas in two other neonates (Ehren et al., 1983). Shah et al. (1987) reported a 6-hour-old full-term female infant who died during surgery for repair of a left congenital diaphragmatic hernia and was found to have hemangioma rising from the lobe of the liver in the left thorax. Hepatic hemangiomas have also been described in association with the Beckwith–Wiedemann syndrome, placental chorioangioma, and dysmorphic kidneys (Drut et al., 1992). In the review by Isaacs, capillary and cavernous hemangioma was the most common histology, accounting for 39% of cases, followed by type I hemangioendothelioma (31%), infantile hemangiomas (24%), and angiosarcoma (7%) (Isaacs, 2007).

The second most common benign hepatic tumor that occurs during the perinatal period is mesenchymal hamartoma (Dehner, 1978; Dehner, 1981, Isaacs, 1983; Stocker and Ishak, 1983; Weinberg and Finegold, 1986; Davis et al., 1988; DeMaioribus et al., 1990; Isaacs, 1991; Isaacs, 2007;). Over 33% of cases of mesenchymal hamartomas are diagnosed in infants and about 25% are in newborns. In the review by Isaacs, 23% of hepatic tumors were mesenchymal hamartomas (Isaacs, 2007). In a report by Keeling (1971), five of seven patients with this condition were of the age of 2 months or younger. The lesion was an incidental postmortem finding in three newborns, including one stillborn infant.

The pathogenesis of mesenchymal hamartoma is incompletely understood and, as the name hamartoma implies, it is of a developmental rather than a neoplastic origin (Dehner, 1978, Weinberg and Finegold, 1986). Lennington et al. (1993) have suggested that mesenchymal hamartomas result from anomalous blood supply to a liver lobule, leading to ischemia and subsequent cystic change and fibrosis. Consistent with this premise is the observation that some hamartomas have necrotic centers and are attached to the liver by a pedicle (Lennington et al., 1993). In addition, neither recurrence following complete resection nor malignant transformation has been reported in mesenchymal hamartomas (Dehner, 1978; Isaacs, 1983; Stocker and Ishak, 1983; Stanley et al., 1989). Mesenchymal hamartomas can readily be detected by prenatal sonographic examination (Foucar et al., 1983; Hirata et al., 1990; Wienk et al., 1990; Mason et al., 1992; Garmel et al., 1994; Isaacs, 2007). Most mesenchymal hamartomas are multicystic (70%), with the remainder being either solid or a combination of solid and cystic (Isaacs, 2007). In general, mesenchymal hamartomas are not associated with other congenital malformations (Weinberg and Finegold, 1986), but occasional exceptions have been noted, including Keeling’s (1971), report of excessive oral mucus secretions and an abdominal mass. This infant was found to have a tracheoesophageal fistula with an annular pancreas in addition to the hamartoma. Stocker et al., reported that 5 of their 30 patients with mesenchymal hamartoma had various anomalies and associated conditions (Stocker and Ishak, 1983). Most mesenchymal hamartomas occur in the right lobe of the liver (90%) but up to 10% can be bilateral (Dehner, 1978; Weinberg and Finegold, 1986; Dehner, 1987; Isaacs, 2007). Hepatoblastoma is the leading primary hepatic malignant tumor occurring during the first year of life (Isaacs, 1997; Isaacs, 2007). Over half of all hepatoblastomas are diagnosed in infants, but less than 10% are found in newborns (Keeling, 1971; Exelby et al., 1974; Gonzalez-Crussi et al., 1982; Weinberg and Finegold, 1983; Weinberg and Finegold, 1986; Campbell et al., 1987; Isaacs, 1991). Among the 32 cases of fetal and neonatal hepatoblastomas reported by Isaacs, 9 were diagnosed prenatally (Isaacs, 2007).

Typically, hepatoblastoma presents as an upper abdominal mass arising from a single area, more often from the right lobe of the liver than the left (Figure 111-1). Hepatoblastoma can be detected by antenatal sonography (van de Bor et al., 1985; Orozco-Florian et al., 1991; Garmel et al., 1994; Isaacs, 2007). In one prenatally detected case, a hepatoblastoma was responsible for compression of the inferior vena cava, leading to fetal hydrops and intrauterine death at 36 weeks of gestation (Benjamin et al., 1981). Kazzi et al. (1989) described a similar case in a newborn with hepatoblastoma that was diagnosed antenatally. Hydrops fetalis, consumptive coagulopathy associated with massive hemorrhage into the tumor, and anemia were present at birth in this fetus. Orozco-Florian et al. (1991) reported a fetus with hepatoblastoma detected antenatally that had associated nephromegaly and pancreatic nesidioblastosis consistent with the diagnosis of Beckwith–Wiedemann syndrome; however, the affected neonate did not have either macroglossia or omphalocele. In addition to neuroblastoma and leukemia, hepatoblastoma is one of the rare perinatal malignancies that can metastasize to the placenta and cause fetal death (Bond, 1976; Robinson and Bolande, 1985; Dinmick, 1991). A broad range of congenital anomalies and malformation syndromes have been reported to occur in association with hepatoblastoma. Hemihypertrophy can occur in as many as 2% to 3% of affected patients. Beckwith–Wiedemann syndrome and familial intestinal adenomatous polyposis (FAP) are the most common associated syndromes (Geiser et al., 1970; Landing, 1976; Fraumeni et al., 1978; Dehner, 1981; Weinberg and Finegold, 1986; Li et al., 1987; Kazzi et al., 1989; Hartley et al., 1990; Giardiello et al., 1991; Orozco-Florian et al., 1991; Greenberg and Filler, 1993; Rubie et al., 1993). Hepatoblastoma, in addition, has been described in siblings in a variety of clinical settings, including in fetal alcohol syndrome, in association with the maternal use of contraceptives, in trisomy 18, in patients with Wilms tumor, and in newborns with adenomatoid malformation of the renal epithelium (Landing, 1976; Khan et al., 1979; Knowlson and Cameron, 1979; Mamlok et al., 1989; Riikonen et al., 1985; Greenberg and Filler, 1993). Aicardi syndrome (infantile spasms, agenesis of the corpus callosum, and multiple ocular malformations) has been described in a 2-month-old female infant with hepatoblastoma (Tanaka et al., 1985).

No clearly defined factors have been implicated in the development of these tumors and the causes of these entities are unknown. Because of the rarity of these lesions, much remains to be learned about the prenatal sonographic findings, natural history, and optimal pregnancy management for these unusual cases.

Tumors of the liver presenting during the perinatal period are rare. Primary hepatic neoplasms account for only 0.5% to 2% of pediatric tumors (Alagille and Odievre, 1979). They comprise 5% of total neoplasms occurring in the fetus and neonate (Dehner, 1978; Wu et al., 1981; Lack et al., 1982; Stocker and Ishak, 1983; Weinberg and Finegold, 1986; DeMaioribus et al., 1990; Samuel and Spitz, 1995; von Schweinitz, 2003; Sallam et al., 2005). Hemangiomas are relatively common, occurring in as many as 1 in 100 newborns and in 1 in 5 premature infants with a birth weight less than 1000 grams (Folkman, 1984; Enjorlas et al., 1990). The specific incidence of hepatic hemangioma is not known. The annual incidence of hepatoblastoma in the United States is estimated to be 0.9 in 1 million children, with a 2:1 male predominance (Young and Jr Miller, 1975; Fraumeni et al., 1978). However Isaacs found a 1.6:1 female ratio in fetal and neonatal hepatoblastomas (Isaacs, 2007). The incidence of mesenchymal hamartoma is uncertain, but there appears to be a male predominance. The prenatal incidence of each of these hepatic tumors is unknown.