British Journal of Obstetrics and Gynaecology March 1981. Vol. 88. pp 329-332

HEPATOBLASTOMA AS A CAUSE OF INTRAUTERINE FETAL DEATH

CASE REPORT

BY

ELIZABETH BENJAMIN, Lecturer Department of Pathology, University of Manchester

Stopford Building, Oxford Road, Manchester M13 9PT

M. LENDON, Senior Lecturer

AND

H. B. MARSDEN, Consultant Department of Pathology, University of Manchester and

Royal Manchester Children’s Hospital, Pendlebury, Manchester

Summary A hepatoblastoma was found in a 36 week stillborn infant. The tumour compressed the inferior vena cava and was the cause of hydrops foetalis. There was also agenesis of the gall bladder. Amniotic fluid alpha-fetoprotein levels at 15 weeks were normal and did not indicate the presence of the tumour.

HEPATOBLASTOMA is a relatively rare tumour of childhood, usually presenting in the first two years of life and showing a male preponderance of 2: 1. It has occurred in siblings and may be familial (Fraumeni et al, 1969; Napoli and Campbell, 1977). In some instances the tumour has been recorded early in the neonatal period and may be associated with other congenital abnormalities. In a proportion of cases, it is undoubtedly prenatal in origin and is capable of considerable growth during intrauterine life.

We report a case of hepatoblastoma in a 36 week old stillborn female infant which pro- duced inferior vena caval compression and hydrops foetalis. Another congenital abnorm- ality was an absent gall bladder. This is the second reported case of intrauterine death associated with a hepatoblastoma, a previous case having been described in the Italian litera- ture (Rua et al, 1979).

CASE REPORT A 37-year-old woman attended the antenatal

clinic in July 1979. She had had two previous normal deliveries in 1964 and 1968.

An amniocentesis was done early in the second trimester because of maternal age. Ultrasonic examination showed a single fetus and biparietal diameter measurements indicated a gestational age of about 15 weeks. Clear amniotic fluid was obtained and the alpha-fetoprotein level was within normal limits for the gestational age, at 20 pg/ml. Cell cultures showed a normal female karyotype 46XX. In the succeeding weeks fetal growth appeared to be maintained and there were no maternal complications.

On examination at the 37th week, however, the fetal heart was absent although it had been heard the preceding week. Uterine contractions had commenced and within a few hours the woman was delivered of a stillborn female infant.

Autopsy findings The female infant weighed 3 . 2 kg, was grossly

oedematous and there was moderate maceration 329

330 BENJAMIN, LENDON AND MARSDEN

with collapse of cranial bones, compatible with intrauterine death of up to seven days. No external malformations were evident.

The peritoneal cavity contained blood stained fluid. The liver was enlarged and weighed 190 g. The right lobe contained a well circumscribed mass, 7.5 cm in diameter, which was composed of coalescent tan coloured nodules intersected by bands of fibrous tissue (Fig. 1). The lesion formed a smooth globular swelling on the inferior surface of the right lobe but posteriorly the tumour extended to and compressed the inferior vena cava. The remainder of the liver was free of tumour. The gall bladder was absent and its fossa was occupied by the hepatic tumour. There was considerable autolysis of tissue at the porta hepatis and the extra hepatic bile duct was not identified.

The other organs weighed less than expected for the fetal weight but showed no significant abnormalities. The placenta was pale and weighed 810 g. There were patchy fibrin plaques on the fetal surface. The umbilical cord had a battledore insertion and was also pale and markedly oedematous.

Microscopic findings The mass in the liver was a mixed epithelial

and mesenchymal hepatoblastoma. The epithelial element, which showed marked autolysis, was composed of lobules of varying size intersected by fibrous septa (Fig. 2). In better preserved areas, fetal and embryonal type cells were discernible. The fibrous septa contained pro- liferating bile ducts, dilated vascular channels

FIG. I Hepatoblastoma within right lobe of the liver. The inferior vena cava (arrowed) is separated from the tumour by hepatic parenchyma on the inferior surface.

FIG. 2 Trabeculae of epithelial cells and adjacent fibrous septum taken from a more

viable part of the tumour. Haematomylin and eosin. ( x 240).

HEPATOBLASTOMA AND FETAL DEATH 331

and many calcific foci. Bile ducts at the periphery of the tumour contained bile. Areas of mesenchy- ma1 tissue and islands of osteoid were prominent, the osteoid being present both within epithelial lobules and in mesenchymal tissue (Fig. 3). Vascular invasion by the tumour was evident in several areas. Small foci of extramedullary haemopoiesis were scattered throughout the tumour. The non involved liver showed no evidence of antecedent disease.

There were no demonstrable metastases to the other organs. The placenta showed patchy perivillous fibrin deposition and occasional hydropic villi but contained no tumour deposits.

DISCUSSION The occurrence of hepatoblastoma in early

infancy and its association with other mal- formations has been described (Ishak and Glunz, 1967; Fraumeni et al, 1968; Filippi and Mckusik, 1970), but the simultaneous congenital

teratogenic and oncogenic influences are not well understood. The reported malformations have included hemihypertrophy, macroglossia, exom- phalos, Meckel’s diverticulum, unilateral absence of adrenal gland and renal agenesis (Ishak and Glunz, 1967; Fraumeni et al, 1968). Some of these may well be coincidental but others like hemihypertrophy have occurred in several cases. Furthermore, hemihypertrophy, macroglossia and exomphalos form part of the Beckwith- Weidemann syndrome known to be associated with an increased incidence of childhood neo- plasms, especially Wilms’ tumour, adrenocortical carcinomas and liver tumours (Filippi and Mckusik, 1970).

The gall bladder was absent in our case and this has not been described before with a hepatoblastoma. Agenesis of the gall bladder is a rare though usually asymptomatic abnormality, the defect originating between the 4th and 6th week of intrauterine development (Gray and

FIG. 3 An island of osteoid tissue with entrapped epithelial tumour cells. Masson trichrome. ( x 200).

332 BENJAMIN, LENDON AND MARSDEN

Skandalakis, 1972). The tumour occupied the site of the gall bladder fossa but there was no trace of the gall bladder within it. Both defects may have arisen at the same period of intra- uterine development.

Epidemiological studies have suggested a greater role for environmental influences than genetic factors in the early peak incidence of childhood liver tumours (Fraumeni et al, 1968). In the case reported by Rua et al (1979) of intrauterine fetal death associated with a hepatoblastoma, the mother had a cholecysto- gram and an abdominal X-ray examination for episodic abdominal pain, early in the first trimester. Likewise the development of hepato- blastoma in an infant whose mother had inadvertently taken progestational steroids throughout the first trimester (Otten et a,, 1977) is of interest because of the association between benign liver cell adenomas and young women taking contraceptive pills (Baum et al, 1973; Edmondson et al, 1976). However, in our case, as in the majority of infantile cases, there were no clearly defined factors which could be implicated in the prenatal development of the tumour.

Of special interest in this case was the normal amniotic fluid alpha-fetoprotein concentration. All reported childhood cases of hepatoblastoma have consistently shown elevated serum alpha- fetoprotein levels of several thousand ng/ml (Anthony, 1979) and it seems likely that the fetal tumour would also be associated with increased production. Regrettably maternal serum alpha- fetoprotein was not estimated in this case. However, since hepatoblastomas can be familial (Fraumeni et al, 1969; Napoli and Campbell, 1977), tests for alpha-fetoprotein may be

Received July 21,1980/Accepted September 9, 1980.

justified in pregnant women who have previously had a child with this tumour.

ACKNOWLEDGEMENTS We are indebted to Dr G. Faulkner for

providing the clinical details.

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