Neuroblastoma

Original Editors - Colleen Mathews from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Colleen Mathews, Lucinda hampton, Khloud Shreif, Elaine Lonnemann, Admin, Fasuba Ayobami, Kim Jackson, Tony Lowe, Evan Thomas, WikiSysop and Wendy Walker

Introduction

Neuroblastoma is the most common solid tumour of childhood.

Image 1: Giant neuroblastoma in an Ethiopian shepherd child

It is almost exclusively a childhood cancer occurring most commonly between the ages of 0-5 years. Neuroblastomas are cancers that start in early nerve cells (called neuroblasts) of the sympathetic nervous system. This means that tumours can be found anywhere along this system; most commonly (about 50%) start in the adrenal glands (above the kidney), or near the spine, chest, neck or pelvis.

Rarely, a neuroblastoma has spread so widely by the time it is found, doctors can’t tell exactly where it started.

Due to the high variability in its presentation, clinical signs and symptoms at presentation can range from benign palpable mass with distension to major illness from substantial tumor spread.

This video (3 minutes) is of the common symptoms of neuroblastoma

Epidemiolgy

The tumours typically occur in infants and very young children (mean age of presentation being ~22 months) with 95% of cases diagnosed before the age of 10 years. Occasionally, they may be identified antenatally or immediately at birth.

Image 2: STAGE IV-S NEUROBLASTOMA This infant has massive hepatomegaly due to metastatic neuroblastoma. Intra-abdominal pressure is partially relieved by a silastic pouch.

Etiology

There are no known reasons as to why this cancer occurs and there are no clear environmental links. Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline.

There are rare cases where neuroblastoma runs in families due to a genetic mutation, but in most cases there is no known genetic cause.

Characteristics/Clinical Presentation

Raccoon eyes

Neuroblastoma presents in a variety of forms based upon the location of its  manifestation and the size of the tumor.. Presentation is typically with pain or a palpable mass and abdominal distension. The neuroblastoma presentation changes if cancer has spread (metastasis), and if the tumor secretes hormones. At the time of the patient's diagnosis, neuroblastoma cells have already spread to other parts of the body 73% of the time due to local mass effect.

Orbital and skull vault neuroplastoma

Other accompanying syndromes include:

• Hutchinson syndrome: skeletal metastases may present with skeletal pain or limping and irritability or proptosis with periorbital and cranial bumps.
• Pepper syndrome: hepatomegaly due to extensive liver metastasis
• Blueberry muffin syndrome: multiple cutaneous lesions
• Opsomyoclonus: rapid, involuntary conjugate fast eye movements
• Proptosis and periorbital ecchymoses ("raccoon eyes"): orbital metastases

This video (3 minutes) is of the common symptoms of neuroblastoma

Location

Neuroblastomas arise from the sympathetic nervous system. Intra-abdominal disease (two-thirds of cases) is more prevalent than intrathoracic disease. Specific sites include:

• Adrenal glands: most common site of origin, 35%
• Retroperitoneum: 30-35%
• Coeliac axis
• Paravertebral sympathetic chain
• Posterior mediastinum: 20%
• Neck: 1-5%
• Pelvis: 2-3%

Treatment and Prognosis

Treatment depends on the patient's stage. Localised tumours considered to be 'low-risk' are surgically excised, and patients tend to do very well (see below). In 'high-risk' tumours, a combination of surgery, chemotherapy +/- bone marrow transplantation is employed, unfortunately with poor overall results. In some cases, where tumours are very large, pre-surgical chemotherapy to attempt to downstage the tumour may be administered.

Patients with stage 1, 2, or 4S have a better prognosis. Unfortunately 40-60% of patients present with stage 3 or 4 diseases 4. For advanced disease, the age of the child is most important.

Stages of Neuroblastoma

The International Neuroblastoma Staging System (INSS) based on surgical resection is used to stage neuroblastomas in the United States.

Stage 1: The percentage of children diagnosed at this stage is 21%.

Stage 2: The percentage of children diagnosed at this stage is 15%

Stage 3: The percentage of children diagnosed at this stage is 17%.

Stage 4: The percentage of children diagnosed at this stage is 41%.

Stage 4S: The percentage of children diagnosed at this stage is 6%.

Poor prognostic factors: later age of onset: >18 months; higher stage: particularly in the presence of metastasis; N-Myc mutation; chromosome 1p deletion; unfavourable Shimada histology index

Better prognostic factors: TRK-A expression

Diagnosis

Neuroblastoma may be difficult to diagnose as symptoms often do not become apparent until the tumour has reached a certain size. Even then symptoms may be subtle and similar to other more common non-serious childhood diseases. As a result it often takes some time before the final diagnosis of neuroblastoma is made.

The clinical presentation along with initial laboratory testing, such as complete blood count, serum electrolytes, liver function tests, chest radiograph, urine or serum catecholamines may show abnormalities. Imaging such as CT scan (neck, chest, abdomen), ultrasound, MRI, iodine-metaiodobenzylguanidine (MIBG) scan, and fluorodeoxyglucose positive emission tomography (FDG-PET) can be utilized for the detection of primary or secondary tumors. The confirmation of neuroblastoma can only be done by biopsy from a specimen obtained from a tumor or bone marrow.

Summary

Neuroblastoma is a rare abdominal tumor in young children. However, if the diagnosis is missed, the tumor is fatal. Hence, the diagnosis and treatment of neuroblastoma are best managed by an interprofessional team that includes a pediatrician, a pediatric surgeon, oncologist, radiation therapist, social workers, pharmacist, dietitian, and specialty care nurses. A team dedicated to childhood cancers is vital as these patients have special needs. All cancer treatments can stunt growth, and hence, a dietitian should be involved early in the care.

Physical Therapy Management

Advances in treatment have led to an increase in the number of cancer survivors. However, childhood cancers are associated with a lot of late effects, such as impaired growth and development, cognition, neurological function, musculoskeletal, cardiopulmonary function, and secondary tumors. Children also experience impaired physical fitness owing to chemotherapy, radiation therapy, and surgical intervention. It includes decreased muscle strength and cardiopulmonary function, fatigue, and altered physical function. Incorporating exercises soon after treatment can improve cardiopulmonary and musculoskeletal function and increase the opportunities for participating in recreational activities.

Image 5: Wiihab

Quality of life is an important theme when it comes to treating children with neuroblastoma and any form of childhood cancer. Side effects of the cancer treatment/medication (chemotherapy, radiation, etc.) and symptoms of cancer itself can lead to a risk of musculoskeletal and neurological issues and psychosocial changes eg Neurological changes including (peripheral neuropathy and radiculopathy); Musculoskeletal changes (disuse atrophy and joint contractures due to radiation fibrosis); Psychosocial (developmental delay, depression and anxiety, social Isolation, behavioral Issues)

Case Reports/ Case Studies

• Case-control study of neuroblastoma in West-Germany after the Chernobyl accident: case-control study.
• Placental infiltration in congenital neuroblastoma: a case study with ultrastructure.
• Paternal occupation and neuroblastoma: a case-control study based on cancer registry data for Great Britain 1962–1999.