DOI:10.2214/AJR.04.1934
AJR 2006; 186:1172-1175
© American Roentgen Ray Society
Simultaneous Presentation of Congenital Neuroblastoma in Monozygotic Twins: A Case of Possible Twin-to-Twin Metastasis
Ibrahim Adaletli1,
Sebuh Kurugoglu1,
Hilal Aki2 and
Ismail Mihmanli1
1 Department of Radiology, Cerrahpasa Faculty of Medicine, Istanbul University,
Istanbul, Turkey 34300.
2 Department of Pathology, Cerrahpasa Faculty of Medicine, Istanbul University,
Istanbul, Turkey 34300.
Received December 21, 2004;
accepted after revision February 22, 2005.
Address correspondence to I. Adaletli
(iadaletli{at}yahoo.com).
Keywords: adrenal gland • congenital neuroblastoma • CT • liver • pediatric imaging
Introduction
Neonatal tumors are rare and comprise 2% of all pediatric malignant tumors.
Neuroblastoma is the most common neonatal solid abdominal tumor
[1]. The tumor originates from
the neural crest cells of the adrenal medulla or sympathetic ganglia.
Concordance for neuroblastoma in monozygotic twins, that is, both twins 1 and
2 having neuroblastoma, presenting either simultaneously or at different
times, rarely has been described. Boyd and Schofield
[2], in their case report and
review of the literature in 1995, presented six cases of concordant twin
neuroblastoma, including their own new case. To the best of our knowledge, we
are unaware of any published English-language literature presenting
simultaneous onset congenital neuroblastoma in monozygotic twins.
Case Report
Two-month-old monozygotic twin girls were admitted to our hospital for
abdominal distention. They had been asymptomatic during the first 2 months of
life. They were born by cesarean delivery at 39 weeks' gestation with a single
monochorionic placenta, after an uneventful pregnancy, to nonconsanguineous
parents with no relevant family history. Maternal history (27 years old,
gravida 2, para 3) and prenatal sonography at 16, 24, and 32 weeks' gestation
were unremarkable. Twins 1 and 2 at birth weighed 2,950 and 3,200 gm,
respectively. During physical examination, both twins were pale and tachypneic
with a pulse rate of 140-146 per min. Their abdomens were markedly distended.
There were no skin lesions. Abdominal sonography of twin 1 showed a left
adrenal, well-defined, thick-walled cystic mass measuring 2.5 x 3
x 2.5 cm and massive hepatomegaly with numerous widespread hyperechoic
nodules (Figs. 1A and
1B). Twin 2 showed similar
findings in the liver with massive hepatomegaly and multiple nodules without
any suprarenal mass lesion. In addition, there was massive free
intraperitoneal fluid in both twins. Abdominal CT revealed crescent
calcification (Fig. 1C) of the
left adrenal mass and ring-like contrast enhancement of the liver nodules in
twin 1. CT findings were similar to sonography, and no adrenal mass was
identified in twin 2 (Fig. 2A).
Ascites aspiration cytology and Tru-Cut biopsy of the liver under sonography
guidance were performed on both twins. On sectioning of the Tru-Cut biopsy,
the tumor was composed of nests and sheets of small cells with fibrillary
background, with hyperchromatic nuclei and scanty cytoplasm (Figs.
2B and
2C). The tumor cells were
positive for neuron-specific enolase, chromogranin, and synaptophysin, but
leukocyte common antigen was negative. On aspiration, the tumor cells had a
dark round or irregular nucleus and long, thin cytoplasmic processes. The
tumor cells were composed of loose clusters. Histopathology and
immunocytochemistry findings were diagnostic for neuroblastoma in both
children. Bone marrow studies showed no tumor cells. Radionuclide bone
scintigraphy was negative. Urinary catecholamine and vanillylmandelic acid
levels were within normal limits. Overall diagnoses of adrenal neuroblastoma
with liver metastasis (stage IVS) in twin 1 and hepatic metastasis
of liver metastasis (stage IVS) in twin 2 were made. Cytogenetic
studies on peripheral blood analysis of both children revealed a normal female
karyotype and lacked rearrangement or deletion of genes. Both twins' tumor
analysis lacked N-myc gene amplification. Chemotherapy consisting of
cyclophosphamide, vincristine, doxorubicin, and etoposide was administered to
the twins for 9 months. The therapeutic course was uncomplicated. They
tolerated and showed excellent response to chemotherapy, and their abdominal
distention resolved after administration of the first round of all the
chemotherapeutic medications. Follow-up sonography, after completion of last
the chemotherapy cycle, showed total resolution of the adrenal mass in twin 1
and liver metastases of both children without any evidence of residual tumor.
The twins are symptom free on follow-up at 16 months.
Discussion
Neuroblastomas can present in many ways. The most frequent presentation
occurs in a child with a primary tumor (abdominothoracic) with or without
metastases. Neuroblastomas can also be multifocal and can be concordant or
discordant (only one of the twins has the tumor) in monozygotic twins
[2-4].
In 1972, Knudson and Strong [5]
suggested two hypotheses that are the most widely accepted etiologic model for
childhood neuroblastoma. The hypotheses invoke both inherited and acquired
genetic defects as the basis for tumor development. In familial (hereditary)
cases of neuroblastoma, the first defect (described as a "hit" by
the author) is an inherited germ line mutation present in all cells of the
body. A second defect or hit occurs postzygotically in only somatic target
cells, the neuroblast. In sporadic (nonhereditary) cases, mutations are
postzygotic events in the same neuroblast. Pathogenesis of multifocal
neuroblastoma has been considered to be multicentric growth of neuroblastoma
nodules or neuroblastoma in situ with a potential for regression or maturation
[4].
Hereditary factors are predominant in neuroblastoma diagnosed in neonates
and infants, whereas nonheritable random mutational genetic events are more
important in neuroblastoma diagnosed after infancy. The cause of the shared
pathology of concordance for neuroblastoma in monozygotic twins has not been
well established. The question is whether the disease is a simultaneous onset
of malignancy in both twins within a twin pair or metastases via placental
vascular anastomoses in utero from one twin with congenital disease to the
second twin. Monozygotic twins may exhibit either mono- or dichorionic
placentation. Only monochorionic placentas share fetoplacental circulations
and thus a possible mechanism of metastases. Histopathologic examination of
metastatic placental tumors revealed tumor thrombi in villous stem vessels and
terminal villi without any gross macroscopic placental lesion
[2]. The massive hepatic
metastases could have arisen as a first-pass effect via blood entering through
the umbilical vein. Systemic metastases also could occur if more umbilical
venous flow with tumor cells enters the right atrium. Fetoplacental metastases
are favored in cases in which one twin within a twin pair manifests a readily
identifiable primary tumor and twin 2 manifests disease either simultaneously
or later without a recognizable primary site. When both twins of a given twin
pair display obvious primary tumors with similar disease extent, a diagnosis
of simultaneous primary neuroblastoma is favored.
With the introduction of molecular and genetic markers such as
N-myc, DNA ploidy, and karyotype, clear-cut biologic markers now are
available to aid in clarifying simultaneous primary tumors versus metastatic
spread from one twin to the other
[2]. If concordance for
congenital neuroblastoma in monozygotic twins exhibits different molecular and
genetic markers, then synchronous primary tumors are favored. If the markers
from each twin are identical, then fetoplacental metastases are favored.
The prognosis for patients with neuroblastoma depends on the biologic
behavior of the tumor cells and the stage of diagnosis. Molecular analysis has
revealed that there are several biologic factors such as N-myc gene
amplification, NTRK1 expression, Ha-ras p21 expression, DNA
ploidy pattern, and telomerase activity
[4,
6,
7]. Although we were unable to
investigate the molecular and genetic markers because of inadequate Tru-Cut
biopsy material, no karyotype anomaly, rearrangement, or deletion of genes was
seen on peripheral blood analysis. In our case, there were both primary tumor
and hepatic metastases in twin 1, whereas twin 2 had hepatic metastases
without a primary tumor site (first-pass effect). In addition, the response to
therapy in both twins was identical. These findings suggest that this case is
a concordant congenital neuroblastoma in monozygotic twins with fetoplacental
twin-to-twin metastases.
References
- Bader JL, Miller RW. US cancer incidence and mortality in the first
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- Boyd TK, Schofield DE. Monozygotic twins concordant for congenital
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- Kushner BH, Helson L. Monozygotic siblings discordant for
neuroblastoma: etiologic implications. J Pediatr1985; 107:405
-409[Medline]
- Hiyama E, Yokoyama T, Hiyama K, et al. Multifocal neuroblastoma:
biologic behavior and surgical aspects. Cancer2000; 88:1955
-1963[Medline]
- Knudson AG Jr, Strong LC. Mutation and cancer: neuroblastoma and
pheochromocytoma. Am J Hum Genet 1972;24
: 514-532[Medline]
- Noguera R, Canete A, Pellin A, et al. MYCN gain and MYCN
amplification in a stage 4S neuroblastoma. Cancer Genet
Cytogenet 2003; 140:157
-161[CrossRef][Medline]
- Peterson S, Bogenmann E. The RET and TRKA pathways collaborate to
regulate neuroblastoma differentiation. Oncogene2004; 23:213
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Introduction
Case Report
