Keywords neuroblastoma - pediatric oncology - urinary bladder - pediatric tumors
Introduction
Neuroblastoma (NBL) is the commonest solid tumor of infancy and the second most common
extracranial malignant tumor of childhood.[1 ] Most commonly occurring in the abdomen in 65% of cases, NBL can also develop in
the paraspinal sympathetic ganglia at other sites including the chest (20%), neck
(5%), and pelvis (5%)[2 ]
. Forty percent of symptomatic patients are younger than 1 year at the time of diagnosis
and with a slight male predominance (1.2:1).[1 ] NBL affects 1 in 7,000 children and is thought to be responsible for 15% of oncology-related
mortality in childhood.[3 ] We report an unusual case of NBL arising from the dome of the urinary bladder (UB)
of a 7-month-old infant. To the best of our knowledge, this is only the ninth reported
case of a neuroblastic tumor originating primarily from the UB.
Case Report
Our patient is a 7-month-old previously healthy boy, who was referred to our tertiary
center with an incidental finding of a pelvic mass on ultrasound (US) that was performed
as part of the investigative pathway for the febrile urosepsis he was being managed
for.
Clinical examination and laboratory work-up were essentially unremarkable. US showed
a well-circumscribed, solid, polypoid mass arising from the UB fundus, measuring 2
cm in diameter, with hypervascularity on color Doppler ([Fig. 1A ]). Magnetic resonance imaging (MRI) showed a (20 × 18 × 17 mm) well-defined, homogenous,
solid mass arising from the middle/left side of the dome of UB ([Fig. 1B ]). A cystoscopic biopsy was attempted but proved to be difficult as the mass was
completely submucosal and not clearly visible.
Fig. 1 (A ) Incidentally discovered urinary bladder mass. (B ) Magnetic resonance imaging (MRI) showing solid mass arising from the urinary bladder
fundus (arrow ).
We proceeded to excisional biopsy through an extended suprapubic incision. The dome
of the UB was opened, and the tumor felt elastic, firm, and homogenous ([Fig. 2 ]). The mass was excised completely with grossly negative margins, and the recovery
period was uneventful. Histopathology was consistent with a completely excised, poorly
differentiated NBL with low mitosis–karyorrhexis index and favorable histology, as
per Shimada's classification. Multiplex ligation dependent probe amplification analysis
showed no evidence of proto-oncogene N-myc (MYCN) amplification or any segmental chromosomal
abnormalities.
Fig. 2 Intraoperative view of the urinary bladder mass.
Further assessment was made for metastatic disease, including bone scan, bone marrow
biopsy, and MIBG (metaiodobenzylguanidine) scan, which were all negative. Urine creatinine,
HMMA (4-hydroxy-3-methoxy mandelic acid)/creatinine, and homovanillic acid (HVA)/creatinine
ratios were all within normal limits.
Due to favorable prognostic factors, our patient was classified as a very low risk
group according to the International Neuroblastoma Risk Group staging system (INRGSS)
and was treated by surgical excision only. Annual follow-up with clinical examination
and two MRI scans performed after 1 and 3 years postoperatively revealed no evidence
of recurrence or residual tumor. The patient remained asymptomatic throughout and
was discharged from follow-up after 5 years.
Discussion
NBL is the most common extracranial solid tumor of childhood.[4 ] NBL of the UB, however, is an almost unknown entity. As it originates from neural
crest cells, NBL can occur anywhere along the sympathetic chain and has a median age
of presentation of 18 to 23 months.[1 ]
[5 ] Most primary tumors occur in the abdomen in 65% of cases, commonly from the adrenal
glands, and 15 to 20% occur in the thorax, whereas pelvic presentation is seen in
approximately 5% of cases.[2 ]
[6 ] Rare sites of primary NBL include the orbit, lung, and genitourinary tract.[7 ] Tumors arising from the retroperitoneal or pelvic space are more frequently diagnosed
on routine mass screening such as the Japanese program, which started in 1984, in
which urine samples from infants aged 6 months were tested for HVA and vanilmandelic
(VMA) acid by high-performance liquid chromatography.[8 ]
[9 ]
Other than cases diagnosed by screening, bladder NBL can present with microscopic
hematuria and/or the presence of a palpable mass on physical examination.[10 ]
[11 ] Our patient was asymptomatic, most likely due to the early incidental diagnosis.
Literature review suggests eight other similar reported cases to date. Six patients
were under 15 months of age,[12 ] whereas the other two patients were 3 and 5 years of age, respectively.[13 ]
[14 ] Interestingly, in six out of eight reported cases, the masses originated from the
dome of the UB.[12 ]
[13 ]
[14 ] The two other reported sites of pathology were the lateral and the anterior walls
of the UB.[12 ]
[13 ]
[14 ] All pathological subtypes of the NBL spectrum were described with four patients
exhibiting poorly differentiating NBL, one case of stroma-poor differentiating NBL,
one ganglioneuroblastoma (GNBL), a single ganglioneuroma (GN) and one case was not
specified.[12 ]
[13 ]
[14 ]
[Table 1 ] summarizes the histological classification, MYCN amplification, chromosomal abnormalities,
and treatment given for the described cases. All cases had a good outcome with no
reported mortality.[12 ]
[13 ]
[14 ]
Table 1
Characteristics of eight reported cases of neuroblastoma of the urinary bladder
Case
Age
Histology
Shimada's classification
MYCN
Chromosomal deletions
Ploidy
Surgery
Chemotherapy
1
3 mo
Poorly differentiated NBL
Favorable histology
Amp
Yes
Diploidy
Partial cystectomy
Adjuvant after recurrence
2
4 mo
Poorly differentiated NBL
Favorable histology
NA
–
Aneuploidy
Partial cystectomy
Adjuvant
3
4 mo
GNBL
–
–
–
–
Partial cystectomy
No
4
7 mo
Poorly differentiated NBL
Favorable histology
NA
–
–
Partial cystectomy
No
5
8 mo
Poorly differentiated NBL
Favorable histology
NA
No
–
Partial cystectomy
No
6
15 mo
NBL (not specified)
Favorable histology
NA
–
–
Partial cystectomy
Neoadjuvant
7
3 y
Differentiating NBL
Favorable histology
NA
–
–
Partial cystectomy
No
8
5 y
GN
–
–
–
–
Transurethral resection
No
Abbreviations: Amp, amplified; GN, ganglioneuroma; GNBL, ganglioneuroblastoma; MYCN,
proto-oncogene N-myc; NA, not Amplified; NBL, neuroblastoma.
The preoperative staging system in NBL is the INRGSS of 2009, which has simplified
the staging into L1, L2, M, and MS.[15 ] By a combination of postoperative staging and other prognostic factors including
age, Shimada grade, histological features, and genetics, patients are grouped into
four prognostic risk groups: very low, low, moderate, and high.[15 ]
[16 ] Postsurgery, NBL is classically staged from 1 to 4 according to the 1993 revised
International Neuroblastoma Staging System.[17 ]
NBL is known to exhibit the highest rate of spontaneous regression among malignant
tumors.[18 ] Ghazali[19 ] first reported a series of pelvic NBL that underwent spontaneous regression and
maturation. Subsequent studies adopting a watchful waiting approach in patients with
NBL detected by screening or during infancy report high rates of regression.[20 ]
[21 ] Therefore, although active intervention is the mainstay of treatment, a wait-and-see
approach avoiding surgical procedures and chemotherapy in localized NBL diagnosed
in early infancy has been suggested.
Treatment strategies for NBL include surgery, chemotherapy, and/or radiation. Stem
cell transplant and immunotherapy are reserved for advanced or recurrent disease.
Low and intermediate risk groups have a 95% survival rate with the use of surgery
and/or chemotherapy. High-risk groups with combination therapy have a survival between
40 and 50%.[5 ]
Our patient was stage L1 by INRGSS and because of the favorable prognostic factors
was put in the very low-risk group, which is amenable to treatment by surgical excision
solely. Annual clinical examination and two postoperative MRI scans revealed no evidence
of recurrent or residual tumor. We discharged the patient after 5 years of follow-up.
Conclusion
Although rare, NBL should be considered in the differential diagnosis of pediatric
urinary bladder masses, especially when arising from the dome.
