Neuroblastoma imaging

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 3 rd 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  131 I 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),   68 Ga 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 2 nd yr,6 mnthly onwards MIBG: 3 monthly (high risk),6 month(stable)