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.

File:Neuroblastomacells.jpg

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.

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.

This 7 minute video is all about Neuroblastoma, good viewing.

Stages of Neuroblastoma

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

The primary tumor is located and isolated to one area of the body. The lymph nodes bilaterally are negative for cancer. The neuroblastoma cancer in this stage can be removed by surgery. Microscopic residual cancerous tissue may remain after the removal of the tumor.

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

• 2A: The primary tumor at this stage is confined to one area. However, it cannot be completely removed through surgery because of its larger size, proximity to other organs, or general location. The lymph nodes are negative bilaterally on both sides of the body for metastases.
• 2B: The primary tumor at this stage is confined to one area of the body. The tumor may or may not be completely surgically removed. The lymph nodes on the side of the body where the tumor is located are positive for metastasis of neuroblastoma. The lymph nodes on the opposite side of the body are negative for metastasis.

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

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

This stage of presentation occurs when neuroblastoma cells are found in the distal lymph nodes, liver, bone marrow, or additional organs.

Stage 4S: The percentage of children diagnosed at this stage is 6%. The presentation at this stage is typically found within infants. The primary tumor is isolated to one area of the body, but the tumor has metastasized to other regions of the body such as bone marrow, liver, or skin. Bone metastasis is rare in this category, with less than 10%.

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.

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

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 the following musculoskeletal and neurological issues.

• Neurological changes including (peripheral neuropathy and radiculopathy)
• Musculoskeletal changes (disuse atrophy and joint contractures due to radiation fibrosis)
• Developmental Delay
• A generalized effect of a decrease in endurance, increase fatigue and decreased strength

The effects are not isolated to physical losses but also include psychosocial changes as well. The following are included in psychosocial considerations when treating a child with neuroblastoma and cancer.

• Depression and anxiety
• Poor self-esteem
• Loss of purpose (due to the fact that most have changes in school life, social 
  
  changes, and family life)
• Social Isolation
• Behavioral Issues

Research has also found late effects of childhood cancers including the following presentations.

• Sensory changes (eyesight changes and hearing loss)
• Developmental Changes (learning disabilities and functional deficits)
• System Changes (reproductive issues, cardiopulmonary disease, osteoporosis, uneven growth of limbs, and decreased overall growth)
• Increased risk of secondary cancer

The above presentations are important in screening and for determining the physical therapy  treatment of a child who presents with cancer or neuroblastoma. Physical therapy treatment should include a variety of considerations to address the limitations or deficits of the individual patient. When it is possible therapists can utilize group therapy to decrease social isolation and to develop psychosocial benefits. Wii rehabilitation treatment can address many deficits in the child with cancer such as balance, strength, and endurance.

Contraindications for Aerobic Exercise Laboratory Values:

Platelet Count	<50,000/mm3
Hemoglobin	<10 g/dl
White Blood Cell Count	<3000/mm3
Absolute Granulocytes	<2500/mm3

Overall, PT treatment has been proven through research to benefit the quality of life in a cancer patient of either a terminal or treatable diagnosis.

Case Reports/ Case Studies

• Retroperitoneal Mass with Intradural Extension: Value of Magnetic Resonance Imaging in Neuroblastoma: diagnostic oncology case study.
• 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.
  

Resources

• Mayo Clinic
• Medscape
• children's Neuroblastoma Cancer Foundation.
• American Cancer Society.
• National Cancer Institution