multimodal imaging findings of a case of neuroblastoma

1. NEUROBLASTOMA
DR PRASUN DAS, MBBS
RADIOLOGY RESIDENT,NRSMCH
a case presentation

2. CLINICAL SCENARIO
• 16 MONTH ,BOY
• 1 month of recurrent fever,poor appetite and lethargy. Mom
recently noticed a distended belly.

3. • Abdominal radiograph
• Large soft tissue density in the left upper
quadrant displacing bowel inferiorly. No
calcifications are identified.

4. ULTRASOUND
Large heterogeneous, solid intra-abdominal mass. It appears to arise from the left
retroperitoneum and causes substantial mass effect on the left kidney without
appearing to arise from the left renal parenchyma.

5. CT SCAN
1.Large(13.2*8*10.2
CM) heterogenously
enhancing mass
compressing the left
kidney.
2.Cavernous
transformation of the
portal vein likely
secondary to
obstruction by mass.
3. Ascites.

6. • MOST PROBABLE DIAGNOSIS: NEUROBLASTOMA FROM LEFT SUPRARENAL
GLAND
• DIFFERENTIAL:
• 1. WILMS TUMOUR
• 2.RHABDOMYOSARCOMA
• 3.GANGLIONEUROBLASTOMA
• 4.ADRENAL CORTICAL TUMOUR(FUNCTIONING)

7. Neuroblastoma, poorly
differentiated, high power view of
Homer-Wright pseudorosettes
(H&E, X400)
MYCN amplification, deletion of 1p36, unbalanced gain of 17q, and deletion
of 11q—poor
anaplastic lymphoma kinase (ALK), protein tyrosine phosphatase nonreceptor type
11 (PTPN11), α-thalassemia X-linked intellectual disability (ATRX), MYCN,
and NRAS oncogenes
Immunohistochemical stains
for biologic markers such as
neuron-specific enolase, S-100
protein, and chromogranin

8. • BIOCHEMICAL INVESTIGATIONS:
CBC TO RULE OUT BONE MARROW INVOLVEMENT
A SINGLE URINE TEST FOR VMA/HVA[normal= <25(35)mg/g
creatinine]
>/= 3 SD HIGHER IN URINARY CATECHOLAMINE LEVEL
Serum LDH level
Latest: 1. plasma 3-methoxytyramine
2. Normetanephrine
3. Plasma free 3 orthomethyl dopa
Ratio is 7.2 times higher in
MYCN amplification

9. • Other investigations :
• 1. chest x ray – for mets in lung
• Splaying of the ribs and rib erosion (with thoracic neuroblastoma)
• Widening of the paraspinal line can be seen secondary to
retrocrural extension of retroperitoneal neuroblastomas.
Bone metastases - irregular lucencies or lytic
lesions in the metaphysis or submetaphyseal
bone
a mass in the right thorax behind the
heart. splaying and thinning of the ribs
in the lower rib cage on the right

10.  SKULL XRAY:
LYTIC>SCLEROTIC
SUTURAL DIASTASIS(DURAL METS)
CLASSIC HAIR ON END (AGGRESSIVE VARIANT)
Intraspinal extension of neuroblastomas can be seen on
radiographs. Lateral views of the spine may show widening of
the neuroforamina. Vertebral-body scalloping, erosion of the
pedicles, and scoliosis(MRI IS BEST)
 MRI
 NUCLEAR SCAN
 EXCISION F/B HISTOLOGY WITH IHC & CYTOGENETICS
Lateral view of the skull shows
widening of the coronal sutures and
multiple lucencies in the parietal
and frontal bones of the skull in this
patient with metastatic
neuroblastoma.

11. • most common extracranial solid childhood malignancy and are the third
commonest childhood tumor after leukemia and brain malignancies.
• 95% of cases diagnosed before the age of 10 years
• Abd: sudden increase of lump,VIP induced diarrhoea
• Pelvic:incontinence,LL edema
• Thoracic: Horner,SVC syn.,Subacute paraplegia
• S/S: OPSOCLONUS,BLUEBERRY MUFFIN,RACOON EYES,PEPPER
• HUTCHINSON SYNDROME
• M/C EXTRADRENAL: ORGAN OF ZUCKERKANDL>CELIAC AXIS
• a/w-Beckwith-Wiedemann syndrome,DiGeorge syndrome,Hirschsprung disease
• neurofibromatosis type 1
• m/c site of mets: cortical bone>lymph nodes>liver
• Aggressive,unencapsulated,heterogenous with encasement
• Peripheral mottled calcification(~85%)
ENIGMATIC DISEASE

12. • USG: screening tool
• Doppler- reduced>increased
• Obstetric usg in 3rd trimester-detect neonatal variant;cystic (diff
from adrenal hemorrhage(m/c)
• 1st alert on liver mets
• CT: tumour extent,encasement,staging
• Partial claw sign
Coronal CT scan of the orbits and
sinuses shows a large, enhancing,
and expansile mass occupying the
ethmoid air cells that is invading
the cribriform plate and breaking
through to the left anterior cranial
fossa. This entity is known as an
esthesioneuroblastoma.

13. Axial nonenhanced T1-weighted MRI shows a hypointense mass in the
retroperitoneum originating from the left adrenal gland. The mass displaces the
left kidney in an anterolateral direction, it extends through the neuroforamen into
the spinal canal, and it displaces the spinal cord to the right. The exact site of
origin of large masses can be difficult to determine. Sympathetic-chain primaries
supposedly invade the spinal canal with greater frequency than do adrenal
primaries
MRI: extradural extension of the tumor and bone marrow involvement and in
identifying diffuse hepatic metastases
displacement of the spinal cord and/or nerve root displacement or
compression and epidural spread of neuroblastoma
hypointense on T1-weighted images and hyperintense on T2-weighted
images.

14. Sagittal T1-weighted and axial T2-weighted
MR images in 2½-year-old girl with medial
retroperitoneal neuroblastoma. Tumor
extends into inferior mediastinum via
infiltration of diaphragm .Tumor completely
encases aorta, celiac artery Inferior vena cava
is displaced and flattened against the mass
 Separation not IDRF
 Contact not IDRF(except renal hilum)
 Flattened vein without visible lumen-IDRF
 Single IDRF
 Multiple IDRF not M disease(multifocal is)

15. • I-131 MIBG has a high principal proton energy (364 KeV). It emits beta particles, thus
giving a large dose of radiation to the patient.I-123 MIBG has a lower principal
photon energy (159 KeV). It also does not emit beta particles, giving less radiation
dose to the patient.I-123 MIBG has a shorter half-life (13 hr) than that of 131I MIBG (8
days), and it must be used the day it is produced, making it more expensive and less
readily available.
• Other tumors which are typically MIBG avid include pheochromocytomas,carcinoid
tumors, and medullary thyroid carcinomas
• 18 F-FDG(undifferentiated), 68Ga DOTATATE(SSTR 2)
• 18 F dihydroxyphenylalanine(DOPA)-HIGHER STAGE
• Prognosis: CURIE SCORE(>2 – poor),SIOPEN SCORE-STAGING IN ADVANCED(MIBG)
FDG PET: MULTIFOCAL
OSSEOUS LESION

16. • INSS: POST SURGICAL, INRGSS: PRE SURGICAL IMAGE BASED
• If disseminated: IDRF of primary to be measured
• Separation, contact-L 1; Encase-L 2[ >270(180 in renal artery)]
• Compression of airway,invasion- L 2

17. NEUROBLASTOMA
• calcification very common: 90%
• encases vascular structures but does
not invade them
• younger age group (<2 years of age)
• poorly marginated
• elevates the aorta away from the
vertebral column
• more commonly crosses the midline,
especially behind the aorta
• more common to have extension into
the chest
• bone metastases are common
(Hutchinson syndrome)
• extension into spinal canal can be
seen
• retroperitoneal lymph nodes are
more often seen
WILMS TUMOUR
• calcification uncommon: 10-15% (10%
rule of Wilms tumor)
• displaces adjacent structures without
insinuating between them, also with
displacement of the renal vessels
• slightly older age group: peak 3-4
years of age
• well-circumscribed
• claw sign with the kidney
• extension into IVC/renal vein
• bone metastases are rare, rather
lung metastases are common
• extension into spinal canal never
seen
• retroperitoneal lymphadenopathy is
uncommon
• higher incidence of hemorrhage

18. • GANGLIONEUROMA
 M/C-POSTERIOR MEDIASTINUM
 MOSTLY ASYMPTOMATIC
 Well circumscribed
 ADC value higher than neuro
 Slower growing
 Non functional
 Older age
• PHEOCHROMOCYTOMA
• M/C-ADRENAL MEDULLA
• Mc extraadrenal- the para-aortic region at the
level of the renal hila (46%)
• elevated plasma and urinary levels of
catecholamines OR
• vanillylmandelic acid (VMA) and metanephrine
• Paroxysmal hypertension, headaches, visual
blurring, sweating and vasomotor changes
• T1-HYPO,T2-HYPER
International neuroblastoma response
evaluation criteria(post neo adjuvant
chemo)

19. 123I-MIBG scintigraphy (d) showed a large area of tracer uptake in the right
adrenal gland (arrow) and disseminated bone marrow involvement of the skull,
long bones, and vertebrae. 99mTc-MDP bone scintigraphy (e) identified
destructive cortical lesions in the axial
and appendicular skeleton (arrowheads).

20. Observation Antenatal diagnosis, age <1 year, stage 4S tumor
Surgery Localized tumor with favorable biological
characteristics
Chemotherapy Low risk, stage 4S disease with life-/organ-
threatening symptoms
Surgery and chemotherapy
High risk or unresectable stage III tumors (induction chemotherapy)
Intermediate risk that is primarily unresectable (moderate
chemotherapy)
High risk metastatic disease (induction +/- postoperative
myeloablative chemotherapy followed by autologous stem cell
rescue)
Radiotherapy High risk disease
Immunotherapy High-risk patients with neuroblastoma can be
maintained in continual remission with anti-GD2-specific monoclonal
antibody therapy combined with GM-CSF with / without IL-2 &
dinutuximab
Future directions ALK-targeted therapy is being explored
• Follow up:
• MIBG,marrow
aspiration: relapse
• Urinary catechol
• US/MR-3 monthly for 1
yr,4 in 2nd yr,6 mnthly
onwards
• MIBG: 3 monthly (high
risk),6 month(stable)