What is an ALK-related predisposition to neuroblastic tumors?

An ALK-related predisposition to neuroblastic tumors is caused by a genetic change in the ALK gene and is associated with the increased likelihood of developing tumors arising from autonomic (i.e. not from consciously controllable) nerve tissues. The tumors concerned are namely neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, which predominantly occur during infancy and childhood. It is also possible for adrenal gland tumors to develop.

How is an ALK-related predisposition to neuroblastic tumors diagnosed?

Clinical Diagnostics

The existence of an ALK-related predisposition to neuroblastic tumors is suspected in a person who exhibits the following:

  • Multiple primary neuroblastic tumors that occur either concurrently or at differing times

  • The occurrence of a neuroblastoma, ganglioneuroblastoma, or ganglioneuroma in more than one family member

Genetic Diagnostics

The diagnosis of an “ALK-related predisposition to neuroblastic tumors” is confirmed by the detection of a mutation – or genetic change – in the ALK gene.

Other Clinical Features

Patients with an ALK-related predisposition to neuroblastic tumors have an increased risk of developing neuroblastic tumors, such as the following:

  • Neuroblastoma: This is a malignant tumor that arises from autonomic (i.e. not from consciously controllable) nerve tissues and has the worst outcome of the tumors described here. Neuroblastomas can occur in the spinal area, in the head and neck area, and in the chest, abdominal, and pelvic area along the autonomic nerve paths and where there are accumulations of autonomous nerve cells. The symptoms vary greatly depending on the location and range from pain to shortness of breath, from urinary tract and intestinal problems to paralysis.

  • Ganglioneuroblastoma: These tumors can either be benign, as with ganglioneuromas, or malignant, as with neuroblastomas. They are usually found in the region of the spine, the trunk, or in the posterior chest area.

  • Ganglioneuroma: This is usually a benign tumor that arises from autonomic (i.e. not from consciously controllable) nerve tissues. Ganglioneuromas mainly occur in the spinal region, in the chest, head, and neck area, and in the adrenal glands. While these tumors often remain asymptomatic, they can in some cases trigger pain or breathing difficulties.

What is the risk of cancer?

If a patient has a mutation – or genetic change – in the ALK gene, the probability that a neuroblastic tumor will develop is presumed to be greater than 50%.

The risk of developing neuroblastic tumors is highest during infancy and decreases with age. With familial neuroblastomas, occur earlier (at the age of 9 months on average) than is the case with neuroblastomas when there is no increased familial incidence (at the age of 2-3 years on average).

In addition, there is a greater risk that multiple primary tumors will occur in familial neuroblastomas compared to the non-familial form. These multiple primary tumors may be bilateral adrenal gland tumors or multiple primary tumors outside of the adrenal glands that form in the cell cluster regions of the autonomic nervous system. The tumors may occur either concurrently or at differing times.

What causes an ALK-related predisposition to neuroblastic tumors?

The ALK-related predisposition to neuroblastic tumors is caused by a mutation – or genetic change – in the ALK gene. This gene encodes for the ALK protein, which functions as a receptor. This receptor controls the propagation and development of immature nerve cells. Now if the gene is present in its altered form, the protein is no longer produced correctly and will be unable to carry out its normal functions correctly, thereby leading to the development of tumors.

Is there a treatment?

Patients with ALK-related neuroblastic tumors should be treated in a pediatric oncology hospital, where the procedure will also be coordinated with the principal investigator of the neuroblastoma study. There are currently no indications that patients with ALK-related neuroblastic tumors are less able to tolerate chemotherapy or radiation therapy or that they react to these therapies with greater sensitivity. In principle, it is even possible to consider the use of ALK inhibitors.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

There are no standard recommendations to date. The following is a possible approach for the early detection of neuroblastic tumors when there is a known ALK mutation:

A clinical examination, abdominal ultrasound, measurement of the catecholamines (neurotransmitters of the autonomic nervous system) VMS and HVS in urine, lung X-rays

  • Every 3 months for children 0-6 years of age

  • Every 6 months for children 6-10 years of age

  • No screening examinations are necessary for children > 10 years of age

Following the successful treatment of a neuroblastic tumor, the surveillance examinations should be continued up to the age of 10 years due to the risk of multiple primary tumors developing.

Self-Care and Support

What should I pay special attention to?

Whenever abnormalities, complaints, or other symptoms occur for the first time, you should go to a doctor right away to clarify whether or not you have a neuroblastic tumor. The sooner it is found, the easier it can be treated and the better the prognosis will be.

Since it is also possible for other tumors – called multiple primary tumors – to develop even after a neuroblastic tumor has been treated successfully, the surveillance examinations need to continue until the age of 10.

Support Groups and Additional Information

Unfortunately, we are as yet unaware of any existing support groups for patients with an ALK-related predisposition to neuroblastic tumors. We will add new information as it becomes available.