Rare Imaging Findings in Pediatric Neuroblastoma

Introduction

A frequent and dangerous childhood cancer that starts in the nervous system is called neuroblastoma. Its behavior can vary, ranging from spreading broadly to improving. Doctors consider characteristics such as the child's age, the disease stage, and genetics to select the best course of treatment. Imaging tests, including nuclear imaging, are essential for diagnosing and ongoing surveillance of neuroblastoma. Combinations of chemotherapy, surgery, radiation therapy, stem cell transplantation, and immunotherapy are frequently used in high-risk situations.

What Are the Signs and Symptoms of Pediatric Neuroblastoma?

• Clinical Presentation: Children between the ages of one and five typically exhibit signs of neuroblastoma (NBL), which frequently include a visible abdominal tumor. The clinical presentation has a great deal of variation, including symptoms such as fever, weight loss, bone pain, and abdominal distension. Hormone-related consequences are also common. Extension of the spinal tumor may occasionally result in neurological symptoms or deficiencies in the peripheral nervous system.

• Encephalopathic Symptoms: Encephalopathic symptoms in children with NBL may be associated with either catecholamine-induced hypertension or an immunological response to the tumor. Blindness may occur from orbital metastases (spread to the eye) or compression of the optic nerves.

• Paraneoplastic Disorders: Watery diarrhea and opsoclonus-myoclonus-ataxia syndrome (a rare nerve system condition that often manifests in the second year of life) are two examples of the uncommon (less than two percent) paraneoplastic disorders that NBLs may exhibit. Opsoclonus-myoclonus, which frequently occurs in thoracic malignancies with a better prognosis, is characterized by jerking movements of the eyes and extremities. The generation of vasoactive intestinal peptides by tumors causes diarrhea, which goes away when the tumor is completely removed.

• Incidental Discovery and Screening: NBLs may be unintentionally found during scans performed for other purposes, such as chest radiography or prenatal ultrasounds. Although screening procedures such as urine VMA (vanillylmandelic acid ) and HVA (Homovanillic acid) tests have been employed, their effect still needs to be determined. Japan stopped screening in 1973 because the country's low-stage tumor rate had increased, and there had been no discernible improvement in cure rates.

• Findings From the Clinical Examination: In children with NBL, a clinical examination typically reveals an abdominal mass. Depending on where the tumor is located, other observations could include neurological impairments, dyspnea (shortness of breath), renin-associated hypertension, bowel or bladder dysfunction, or evidence of cord compression. The 'harlequin' sign (uneven facial blushing and sweating) and Horner's syndrome (one side of the brain's nerve supply to the face and eyes is damaged) may occur in conjunction with dysphagia (difficulty in swallowing), stridor (a high pitched respiratory sound), or a neck mass as a symptom of cervical NBLs.

What Are the Clinical Stages of Pediatric Neuroblastoma?

• International Neuroblastoma Staging System (INSS) Classification:

  • Stage 1 and 2: Localized tumors, excised with or without lymph node involvement.

  • Stage 3: Unresectable tumors.

  • Stage 4: Tumors with distant spread.

  • Stage 4S: Localized tumors in infants with limited spread.

• Challenges:

  • Difficulty distinguishing stages, especially in children less than a year.

• Special Categories:

  • Stage 4N: Better prognosis, distant nodal spread without cortical involvement.

• Metastasis:

  • Common Sites: Bone marrow, lymph nodes, liver, and skin.

• Prognostic Factors:

  • Adverse Factors: Osseous metastases (bone spread), tumor resectability, and lymph node involvement.

• Survival Rates:

  • Favorable rates for stages 1, 2, and 4S.

  • Infants less than a year: 80 percent to 90 percent for stage 3, 60 percent to 75 percent for stage 4.

  • Children over one year: 50 percent for stage 3, 15 percent for stage 4.

What Are the Imaging Findings of Pediatric Neuroblastoma?

• A Comprehensive Approach to Staging Neuroblastoma: As a highly diverse juvenile malignancy, neuroblastoma (NBL) necessitates a multimodal imaging-based staging approach. These consist of [123I]meta-iodobenzylguanidine (123I-MIBG), magnetic resonance imaging (MRI), and computed tomography (CT), as well as specialist laboratory tests that look at urine catecholamine levels and bone marrow aspirates. This multi-modal approach is essential because of the various biological types and common metastasis of NBL at the time of diagnosis.

• Symptom and Presentation-Related Initial Imaging: When a kid presents with signs of non-verbal learning (NBL), chest and abdominal radiographs, skeletal films, abdominal ultrasound, or spinal MRI are all part of the first imaging workup. Early indicators are frequently seen on radiographs showing characteristic shadows and calcifications. Ultrasonography (US) is especially helpful for palpable abdominal masses because it provides a detailed view of the tumor's local features, possible displacements, and interactions with surrounding structures.

• MIBG Scan: MIBG is a norepinephrine-like chemical that is taken up and retained in neuroendocrine tumors, especially neuroblastomas (NB). For imaging purposes, it is tagged with either Iodine-131 or Iodine-123. Better image quality makes the I-123 labeled version the preferable choice; nevertheless, when I-123 is not accessible, I-131 is employed. The excretion of MIBG in urine causes the urinary bladder and urinary tract to become extremely active. Normally, the liver absorbs it the most, with lower amounts entering other organs. Increased tracer concentration areas in MIBG scans signify the presence of malignancies; for greater precision, additional imaging modalities such as Single Photon Emission Computed Tomography (SPECT) may be employed. Metastatic illness is defined if MIBG uptake is seen at a distant site. However, a biopsy or other imaging modalities might need to confirm unclear results. Tumor burden and response are evaluated semi-quantitatively using scoring systems that split the body into sections and assign points according to the number of sites impacted and the degree of absorption.

• Bone Scan: A Technetium-99m bone scan is required if the main tumor has been excised or does not absorb the MIBG material. Metastatic lesions in the bone appear as distinct hot areas on this imaging. Blurring close to the growth plate that extends the tracer into the metaphyseal region may indicate metastatic involvement. If uptake is limited to the bones, further imaging techniques or a biopsy should be performed for confirmation.

• Abdominal Mass Screening Using Ultrasonography (US): Since ultrasound is non-invasive, it is a great way to check for palpable masses in children's abdomens. NBLs can have calcifications and usually present as heterogeneous solid lesions that are frequently echogenic. Ultrasound is useful in assessing the local size of the tumor, its proximity to main arteries, and its ability to displace nearby organs such as the kidney.

• Axial Imaging for Detailed Staging Using CT or MRI: CT or MRI axial imaging is essential for a more thorough staging of recently detected NBL. These two modalities reveal the location, size, vascular involvement, and resectability of the main tumor. With benefits including reduced radiation exposure and improved evaluation of bone infiltration, magnetic resonance imaging (MRI) has been more popular in recent years.

• CT Imaging Features: NBLs are characterized by CT imaging as big heterogeneous masses with calcifications, bleeding, or pseudo-necrosis areas that can be easily identified. It is good at showing how tumors can encase and compress large abdominal arteries, which frequently makes it difficult to tell apart the main tumor from a nodal illness that is nearby. Furthermore, CT is a useful tool for identifying metastases to organs, including the liver and lungs.

• Benefits and Features of MRI: MRI is invaluable when defining the heterogeneity of NBL. Variable enhancement patterns, extended relaxation durations, and diffusion-weighted pictures reflecting the diffusion of water protons inside the tumor matrix are captured. MRI is especially helpful when evaluating intricate features such as leptomeningeal dissemination, epidural extension, and the distinct dumbbell-shaped NBLs. It is also helpful in identifying diseases of the bone marrow, which can manifest as diffuse infiltration or nodules.

• Somatostatin Receptor Scintigraphy: Somatostatin receptors are present in some neuroblastoma tissues, and doctors may use this information to identify neuroblastoma using specific chemicals that have been radiolabeled. Imaging investigations can identify these compounds, such as pentetreotide, lanreotide, and octreotide tagged with indium-111. In SPECT tests, they use agents tagged with 99mTc, and in PET scans, they use 68Ga. According to research, Somatostatin receptor-positive neuroblastomas may be less dangerous and have a better prognosis. In cases where MIBG scans are negative for neuroblastoma, somatostatin receptor imaging (SRS) may be explored.

• Overcoming Obstacles in Under-Staging: The medical world is increasingly using MRI with whole-body short-time inversion recovery (STIR) imaging in place of CT because of possible under-staging issues. This substitute lessens the risk of radiation exposure, which is crucial in situations involving minors, and also lessens the necessity for sedative techniques in young patients. This method overcomes the possible drawbacks of CT, especially in identifying tiny regions of cortical degeneration connected to stage 4 NBL.

What Is the Recommended Monitoring Strategy for Children With Neuroblastomas?

Doctors will monitor infants and young children with low-risk pelvic or abdominal tumors that do not appear to spread much with ultrasonography (US). In particular, for tumors in stage 4S where surgery might not be necessary, this aids in tumor monitoring both before and after surgery. Physicians should monitor a child with a high-risk condition using CT or MRI in addition to the US if the child received local radiation.

Monitoring the concentrations of specific chemicals in the blood or urine is insufficient to accurately identify or rule out the tumor's recurrence or progression. Physical examinations and various imaging procedures, such as US, CT, MRI, and MIBG (if the tumor and its dissemination first appeared on MIBG), should be part of routine check-ups.

Imaging studies should be performed after chemotherapy to assess treatment response and determine when surgery should be postponed. In most cases, if the tumor shrinks in response to treatment, it may also become more calcified. With MIBG or MRI, recurrent bone marrow illness following chemotherapy can be reliably identified. Gadolinium is used in MRIs to aid in distinguishing between scarring from inactive tissue and residual disease or recurrence, making the latter easier to see.

Particularly in stage 4S, some neuroblastomas (NBLs) can spontaneously shrink or mature for six to twelve months. It is unclear why this natural process occurs, although it is also observed in stages 1 and 2 of malignancies.

How Is Pediatric Neuroblastoma Treated?

Based on biological traits, age, stage, and other considerations, doctors choose the best course of treatment for neuroblastomas based on their risk level.

• Treatment has been raised for high-risk patients but decreased for low and intermediate-risk patients.

• For stage 2 and low-risk cancers, surgery is sufficient; for stage 3 and intermediate-risk tumors, chemotherapy is added.

• Surgery, chemotherapy, and occasionally bone marrow transplantation are used to treat high-risk malignancies.

• For high-risk cases, survival is frequently less than 15 percent, even with intensive therapy. Chemotherapy can reduce the tumor before surgery, and the timing of the procedure is especially important for stage 3 tumors.

• Treatment options include certain medications and occasionally radiation.

• Future objectives include monitoring and improved treatments, such as antibodies and retinoids.

Conclusion

Physicians employ MRIs, MIBGs, and PET scans, among other studies, to help them understand pediatric neuroblastoma tumors. These examinations aid in precisely determining the type and size of the tumor. Since MRI and MIBG are so effective at identifying these tumors, they are particularly crucial for diagnosis and follow-up. It is difficult to anticipate how effectively a treatment will work or how long the condition will last. Still, medical professionals are trying to improve these predictions by combining genetic, biochemical, and nuclear investigations. Treatments are becoming more individualized to improve outcomes while minimizing side effects, with a reduction in the use of harsh medications for younger children and an emphasis on cutting-edge techniques for high-risk cases.