Clinical Guidance

Individuals with ALK-related neuroblastic tumor susceptibility are at risk of developing a spectrum of neuroblastic tumors that include neuroblastomas, ganglioneuroblastomas, and ganglioneuromas. These individuals also have a higher-than-average incidence of other primary tumors (e.g., bilateral adrenal tumors, extra-adrenal tumors arising at sites of sympathetic ganglions). Neuroblastic tumors. Risk for neuroblastic tumor development is highest in infancy and decreases by late childhood, with 98% of neuroblastic tumors occurring by age ten years . Individuals with familial neuroblastoma tend to develop tumors at a younger age (average age nine months) than those without familial predisposition (age two to three years) .

Diagnostic Criteria

Suggestive Findings

ALK-related neuroblastic tumor susceptibility should be suspected in probands with:

• A neuroblastic tumor including neuroblastoma, ganglioneuroblastoma, or ganglioneuroma;

• Multiple primary neuroblastic tumors that arise either synchronously or metachronously;

• A family history of one or more relatives with one of these three neuroblastic tumors. Note: Both benign and malignant tumors can occur in the same family.

Management Guidelines

No clinical practice guidelines for ALK-related neuroblastic tumor susceptibility have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ALK-related neuroblastic tumor susceptibility, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. ALK-Related Neuroblastic Tumor Susceptibility: Recommended Evaluations Following Initial Diagnosis

Surveillance Guidelines

Guidelines for the screening of asymptomatic children with familial neuroblastoma – including those with germline ALK activating pathogenic variants – have been published . Surveillance is also recommended for children with a germline ALK activating pathogenic variant who were successfully treated for a neuroblastoma due to risk of developing multiple primary tumors.

Table 5.

ALK-Related Neuroblastic Tumor Susceptibility: Recommended Surveillance