225ASIAN JOURNAL OF SURGERY VOL 26 • NO 4 • OCTOBER 2003 225

03502R

18th Congress of AAPS

Introduction

Neuroblastoma is an embryonic tumour of sympathetic

origin and is known to be one of the most common malig-

nant solid tumours in infancy. The prenatal diagnosis of

neuroblastoma has now become feasible owing to recent

advances in ultrasonography (US). Prenatally diagnosed

neuroblastoma was first reported by Fenart et al in 1983.1

Since then, approximately 100 cases of prenatally diag-

nosed neuroblastoma have been described in numerous

case reports and a few reviews. Cystic neuroblastomas

comprise about 50% of all cases of prenatally diagnosed

neuroblastomas, and the incidence of such tumours is far

greater than that in the postnatal population. In this study,

we report two cases of prenatally diagnosed cystic neuro-

blastoma (PDCN) and also review the pertinent literature,

focusing on the biological findings and clinical course of

such cases.

Address correspondence and reprint requests to Dr. Shinji Tanaka, Department of Pediatric Surgery,Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.E-mail: stanaka@pedsurg.med.kyushu-u.ac.jp • Date of acceptance: 1st May, 2003

Prenatally Diagnosed Cystic Neuroblastoma:A Report of Two Cases

Case reports

Case 1A circular and homogeneous cyst measuring 30 × 20 mm was

identified at the upper pole of the right kidney in a fetus on

routine prenatal US at 33 weeks’ gestation (Figure 1). The size

and contents of the mass did not change thereafter during

pregnancy. A female infant was born by spontaneous vaginal

delivery at 37 weeks. Postnatal US showed no change in the

cystic mass 4 weeks after birth compared to the prenatal

findings. Urinary vanillylmandelic acid (VMA) and serum

neuron specific enolase (NSE) concentrations increased

slightly. The infant underwent total resection of the tumour at

28 days of age. Histological examination revealed a rosette-

fibrillary stage I neuroblastoma based on the criteria of the

International Neuroblastoma Staging System (INSS). The

features were compatible with the favourable group according

to Shimada’s classification.2 This case had no MYCN proto-

Shinji Tanaka, Tatsuro Tajiri, Shin-ichi Noguchi, Keiko Ogita, Yukiko Takahashi,1 Masazumi Tsuneyoshi1 and

Sachiyo Suita, Departments of Pediatric Surgery and 1Anatomic Pathology, Graduate School of Medical Sciences, Kyushu

University, Fukuoka, Japan.

We report two cases of prenatally diagnosed cystic neuroblastoma (PDCN). In the first case, prenatal ultrasono-

graphy (US) at 33 weeks’ gestation showed a 30 × 20 mm cyst at the upper pole of the right kidney. The size and

content of the mass demonstrated no change during pregnancy. Postnatal US showed no change in the cystic

mass 4 weeks after birth compared to the prenatal findings. The infant underwent total resection of the tumour

at 28 days of age. In the second case, a left cystic mass measuring 50 × 40 mm was detected in a fetus in the 37th

week of pregnancy. Postnatal US showed a cystic mass in the left adrenal gland. The US findings showed no

change 18 days after birth and the infant underwent total resection of the tumour at 19 days of age. In both cases,

pathological examination revealed a neuroblastoma and all of the biological prognostic factors were favourable.

Surgical intervention was necessary for a final histological and biological diagnosis to be made. We recommend

that prenatally suspected neuroblastomas should normally undergo surgical intervention, unless tumour size

decreases within about 1 month after birth. [Asian J Surg 2003;26(4):225–7]

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© 2003 Elsevier. All rights reserved.

226 ASIAN JOURNAL OF SURGERY VOL 26 • NO 4 • OCTOBER 2003

■ TANAKA AND OTHERS ■

detection rate of cystic neuroblastomas is high. Cyst-like

lesions are generally easy to detect by US. However, supra-

renal cystic masses can also sometimes turn out to be adrenal

haemorrhages, extrapulmonary sequestration and hydro-

nephrosis. Sauvat et al reported that a histological analysis of

21 suprarenal localized cystic or mixed masses diagnosed

prenatally showed 16 neuroblastomas (76%), two necrotic

masses, one adrenal haemorrhage, one bronchogenic cyst,

and one sequestration.3 The prenatal detection and solid

appearance of a suprarenal mass makes a diagnosis of neu-

roblastoma very likely, but the optimal diagnostic modalities

and treatments for suprarenal cystic masses have yet to be

elucidated.

The literature includes 46 cases of PDCNs, including the

two cases in this study.4–11 After birth, approximately 50% of

PDCNs tended to increase in size, but none of the tumours in

the 46 cases decreased in size preoperatively. Approximately

30% of all prenatally detected neuroblastomas demonstrate an

elevation in urinary catecholamine levels.4 However, urinary

catecholamines were present in less than 10% of cystic

neuroblastomas.4,5 In both of our cases, there was no remark-

able increase in urinary catecholamine concentrations. On the

other hand, metaiodobenzylguanidine (MIBG) scintigraphy

has been reported to be helpful in diagnosing neonatal cystic

neuroblastomas, with a sensitivity of 70% in the 38 neonatal

suprarenal masses tested for MIBG uptake. However, an analy-

sis of the histological findings is necessary to determine the

final diagnosis.

Most PDCNs are localized neuroblastomas without poor

prognostic factors. Of the 46 PDCNs in the literature, 40 cases

were stage I or stage II, five cases were stage IVS, and one case

oncogene amplification and all other prognostic factors

[aneuploid, 1p deletion (–), Trk A expression (+)] were

favourable. The postoperative period was uneventful and the

infant has remained healthy for 2 years after surgery, with no

further treatment.

Case 2A left cystic mass measuring 50 × 40 mm was identified in a

fetus on routine prenatal US at 37 weeks’ gestation (Figure 2).

A male infant was born by spontaneous vaginal delivery at 38

weeks. Postnatal US showed a cystic mass in the left adrenal

gland. There was no elevation in either the urinary VMA or

homovanillic acid concentrations. US showed no change in

the size of the suprarenal cystic mass 18 days after birth and

neuroblastoma was deemed most likely. The infant under-

went total resection of the tumour at 19 days of age. Pathologi-

cal examination revealed a rosette-fibrillary stage I neuroblas-

toma based on INSS classification. This case was considered to

belong to the favourable group according to Shimada’s crite-

ria for histology, and all biological prognostic factors [no

MYCN amplification, aneuploid, 1p deletion (–), Trk A expres-

sion (+)] were favourable. There was no additional treatment.

The neonate did well after surgery and no evidence of either

metastasis or recurrence has been observed during the 1-year

follow-up with US and computed tomography.

Discussion

Neuroblastoma is the most frequent neonatal malignancy.

Cystic neuroblastoma is uncommon and its incidence is

unknown, but in prenatally detected neuroblastomas, the

Figure 1. Prenatal ultrasonography at 33 weeks’ gestation (Case 1).

Figure 2. Prenatal ultrasonography at 37 weeks’ gestation (Case 2).

227ASIAN JOURNAL OF SURGERY VOL 26 • NO 4 • OCTOBER 2003 227

■ PRENATALLY DIAGNOSED CYSTIC NEUROBLASTOMA ■

was stage IV. MYCN amplification and DNA ploidy were

determined in 14 and eight of the 46 resected neuroblastomas,

respectively. MYCN amplification was negative in all cases.

One case was diploid and seven were aneuploid. In both of our

cases, all biological prognostic factors were favourable, as

described previously.

Of the 46 PDCNs reported in the literature, tumour

extirpations of the primary site were performed in 45 cases,

while one case with a stage IV tumour died in the delivery

room. The median age at operation was 20.6 days (range, 1 day

to 9 weeks). In all cases, no postoperative adjuvant therapies

were performed. Follow-up ranged from 2 months to 10 years

(mean, 26.4 months). Regarding the outcome, 40 patients

were alive and disease-free, three patients were alive with

disease, two patients died due to the disease, and the outcome

was unknown in one patient. Of the 45 cases undergoing

tumour extirpation, four patients had tumour recurrence

(3 cases with multiple metastasis, 1 case with local recurrence).

However, none of the four cases demonstrated any of the

established unfavourable factors. Therefore, the reasons for

recurrence are unclear.

In summary, neuroblastoma should be suspected if

prenatally detected suprarenal cystic masses increase or do not

change in size after birth. However, surgical intervention is

necessary to make a final histological diagnosis. It might also

be important to further investigate the biological factors and

identify other new prognostic factors. We recommend that

prenatally suspected neuroblastomas should undergo surgi-

cal intervention, unless the size of the tumour decreases within

about 1 month after birth. In addition, long-term follow-up

for such prenatally diagnosed cases should be conducted

carefully.

References

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2. Shimada H, Chatten J, Newton WA Jr, et al. Histopathologic prog-nostic factors in neuroblastic tumors: definition of subtypes ofganglioneuroblastoma and an age-linked classification ofneuroblastomas. J Natl Cancer Inst 1984;73:405–16.

3. Sauvat F, Sarnacki S, Brisse H, et al. Outcome of suprarenal localizedmasses diagnosed during the perinatal period: a retrospectivemulticenter study. Cancer 2002;94:2474–80.

4. Acharya S, Jayabose S, Kogan SJ, et al. Prenatally diagnosedneuroblastoma. Cancer 1997;80:304–10.

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8. Petit T, Lagausie PD, Ghoneimi AE, et al. Postnatal management ofcystic neuroblastoma. Eur J Pediatr Surg 2001;11:411–4.

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10. Heling KS, Chaoui R, Hartung J, et al. Prenatal diagnosis of congeni-tal neuroblastoma. Analysis of 4 cases and review of the literature.Fetal Diagn Ther 1999;14:47–52.

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