Metastatic Neuroblastoma
Publication date: August 27, 2016 | Updated on September 7, 2016
Report
Diagnosis
Metastatic Neuroblastoma
History
Eight month-old girl. Abdominal mass.
Findings
Large right superior abdominal mass with heterogeneous uptake (SUV max 4.1) and focal hypometabolic areas (necrotic). This lesion measures 6 x 6 x8 cmand shows calcifications on low dose CT. Right kidney is displaced downward. There is focal abdominal uptake in left para-aortic lymphatic area, likely related to lymphadenopathy (SUV max 1.4). Mild heterogeneous axial and appendicular bone marrow uptake.
No other suspicious lesion.
DDx
Neuroblastoma
Adrenocortical tumor
Wilm’s tumor
Discussion
Neuroblastoma is the most common extracranial solid tumor in pediatric population. Most cases are diagnosed before the age of 5, with a median age of 19 months.
This disease is derived from the neural crest cells. Therefore, tumors can develop anywhere in the sympathetic nervous system. The most common primary site is in the abdomen, usually in the adrenal medulla. Other sites include neck, chest and pelvis. This tumor frequently shows calcifications unlike Wilm’s tumor.
Distant metastasis occur in 50% of patients at the time of diagnosis, occurring through both lymphatic and hematologic routes. Most common distant metastatic sites include bone, bone marrow and liver. In bone, there is a predilection of spreading to metaphysis, skull and orbits.
Staging
Initially, criteria for diagnosis and staging were based on the International Neuroblastoma Staging System (INSS)(Table 1). Subsequently, The Children’s Oncology Group (COG) developed a risk stratification scheme, classifying in low, intermediate or high-risk disease based on clinical and biological factors (Table 2). This stratification allows guiding treatment strategies.
Table 1: International Neuroblastoma Staging System
Stage
Description
1
Localized tumor with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumor microscopically (nodes attached to and removed with the primary tumor could be positive)
2A
Localized tumor with incomplete gross excision; representative ipsilateral non-adherent lymph nodes negative for tumor microscopically
2B
Localized tumor with or without complete gross excision, with ipsilateral non-adherent lymph nodes positive for tumor. Enlarged contralateral lymph nodes should be negative microscopically
3
Unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration (unresectable) or by lymph node involvement
4
Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, or other organs (except as defined by stage 4S)
4S
Localized primary tumor in infants younger than 1 year (as defined for stage 1, 2A, or 2B), with dissemination limited to skin, liver, or bone marrow (<10% malignant cells)
Table 2: Children’s Oncology Group (COG) risk stratification scheme
Risk Group
Stage
Age
MYCN Amplification Status
Ploidy
Shimada
Low
1
Any
Any
Any
Any
Low
2a/2b
Any
Non-amplifiedlified
Any
Any
High
2a/2b
Any
Amplifiedlified
Any
Any
Intermediate
3
< 547 days
Non-amplified
Any
Any
Intermediate
3
≥547 days
Non-amplified
Any
Favorable
High
3
Any
Amplified
Any
Any
High
3
≥547 days
Non-amplified
Any
Unfavorable
High
4
< 365 days
Amplified
Any
Any
Intermediate
4
< 365 days
Non-amplified
Any
Any
High
4
365-547 days
Amplified
Any
Any
High
4
365-547 days
Any
Diploid
Any
High
4
365-547 days
Any
Any
Unfavorable
Intermediate
4
365-547 days
Non-amplified
Hyper
Favorable
High
4
≥547 days
Any
Any
Any
Low
4s
< 365 days
Non-amplified
Hyper
Favorable
Intermediate
4s
< 365 days
Non-amplified
Diploid
Any
Intermediate
4s
< 365 days
Non-amplified
Any
Unfavorable
High
4s
< 365 days
Amplified
Any
Any
Roles of PET/CT FDG
There have been some studies investigating the role of PET/CT FDG in the past few years.
Sharp et al. retrospectively evaluated 113 paired 123I-MIBG and FDG PET/CT of 60 patients. They found FDG to be more accurate than MIBG in depicting disease site in stage 1 and 2. However, 123I-MIBG was superior in stage 4, mostly due to better evaluation of bone marrow metastasis.
Melzer et al. retrospectively found usefulness of FDG when 123I-MIBG was negative, discordant with clinical data or inconclusive.
Papathanasiou et al. prospectively investigated 28 patients with refractory or recurrent neuroblastoma. They concluded that PET/CT FDG could not replace 123I-MIBG in high risk neuroblastoma, but was useful in 123I-MIBG negative neuroblastoma which occurs in approximately 10% of cases. They also found association between tumor avidity (SUV max > 5.3) and poorer prognosis.
Lee et al. retrospectively evaluated 50 patients and found that pretreatment FDG PET was an independent prognostic factor. Patient with low FDG uptake (e.g. SUV max <4 inprimary tumor) had better prognosis.
To summarize, 123I-MIBG is still the exam of choice for initial staging and follow-up. FDG PET/CT can be useful when 123I-MIBG is negative. The FDG tumor avidity seems to correlate with prognosis.
References
Maris et al. : Neuroblastoma. Lancet. 2007 Jun 23;369(9579):2106-20
Sharp et al. : 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med. 2009 Aug;50(8):1237-43
Melzer et al. : ¹²³I-MIBG scintigraphy/SPECT versus ¹⁸F-FDG PET in paediatric neuroblastoma. Eur J Nucl Med Mol Imaging. 2011 Sep;38(9):1648-58
Papathanasiou et al. : 18F-FDG PET/CT and 123I-metaiodobenzylguanidine imaging in high-risk neuroblastoma: diagnostic comparison and survival analysis. J Nucl Med. 2011 Apr;52(4):519-25
Mueller et al. : Nuclear medicine and multimodality imaging of pediatric neuroblastoma. Pediatr Radiol. 2013 Apr;43(4):418-27
Lee et al. : Prognostic value of pretreatment FDG PET in pediatric neuroblastoma. Eur J Radiol. 2015 Dec;84(12):2633-9
Irwin et al. : Neuroblastoma: paradigm for precision medicine. Pediatr Clin North Am. 2015 Feb;62(1):225-56