Before continuing our discussion from last month regarding a review of the pediatric NF clinical care guidelines, I’d like to mention that our annual UAB NF Symposium Family Day was held on Saturday, August 24, in the Bradley Lecture Center of the Children’s Harbor Building. Co-sponsored by the UAB Department of Genetics and the Children’s Tumor Foundation (CTF), this half-day, free event provides NF families and patients an opportunity to hear a series of presentations on a range of NF-related topics from clinical experts. Also, the event offers a venue for families to establish a connection with others who are sharing the same journey, which can be especially meaningful for those who are newly diagnosed. The event was a great success, with more than 100 people registered.

Malignancies Related to NF1

In addition to optic gliomas, discussed in last month’s blog, the pediatric NF clinical care guidelines provide a review of the most commonly occurring malignancies in children with NF1; these include malignant peripheral nerve sheath tumors (MPNSTs), pheochromocytomas, and leukemia. MPNSTs represent one of the few life-threatening complications of the condition. These tumors are uncommon in children and occur mostly in teens and young adults, with the lifetime risk between 8% and 13% for those with NF1. Malignant peripheral nerve sheath tumors usually arise from pre-existing plexiform or nodular neurofibromas. Because MPNSTs can be difficult to treat, the focus is on early diagnosis. The clinical care guidelines indicate a possible diagnosis based on any one of the following: persistent unexplained pain, particularly if it progresses in intensity or wakes one from sleep; rapid growth of a tumor; and a change in a tumor from soft to hard.

If a malignancy is suspected based on clinical presentation, an MRI is usually performed. While MRI will not diagnose a malignancy, it can indicate unusually solid areas of a tumor where cells have deteriorated that are characteristic of a malignancy. Based on these results, a positron emission tomography (PET) scan with radiographic computed tomography (PET-CT) or magnetic resonance imaging (PET-MRI) may be performed to determine the tumor’s uptake of radioactive tracer material. Malignant tumors take up more of the radioactive material on the scan, indicating a possible malignancy, though a biopsy needs to be performed for pathological confirmation. Treatment of MPNSTs usually involves surgery, sometimes with accompanying radiation therapy.  Chemotherapy may be used, though if the tumor has spread this is often unsuccessful.

The guidelines also mention other, less commonly occurring pediatric malignancies in NF1, including astrocytomas, a type of malignant brain tumor; rhabdomyosarcoma, a malignant tumor that originates in the soft tissues of the body; pheochromocytoma, a tumor of the adrenal gland; and juvenile myelomonocytic leukemia, a rare type of blood cancer that occurs in young children.

Although pheochromocytoma affects fewer than 5% of people with NF1 and usually occurs in young adults, it’s an important tumor to recognize. A pheochromocytoma causes the irregular and excessive release of the hormones epinephrine and norepinephrine, resulting in symptoms of high blood pressure, rapid heart rate and palpitations, episodes of flushing, and excessive sweating. When these symptoms are present, a blood test is performed to assess the amounts of metabolic byproducts of epinephrine and norepinephrine present in the blood. A positive result requires a confirmatory 24-hour urine collection for measurement of the same substances. If laboratory results indicate a possible tumor, abdominal imaging is performed and other studies, including use of a radioactive tracer. Treatment is surgical and requires careful planning by an experienced surgical team.

>The clinical guidelines also note that breast cancer occurs more frequently in women with NF1 than in the general population, which should be kept in mind as females with NF1 progress into young adulthood. This risk, along with surveillance guidelines, has been discussed in a previous blog about the adult management guidelines.

Neurologic Issues

Migraine headaches are more common in people with NF1 than in the general population. In addition to the primary symptom of headache, migraines may also present with stomachache and nausea in children. The guidelines indicate that clinical judgement should be used in determining whether MRI is needed to determine other causes for headache. Indications for MRI could include: symptoms of increased intracranial pressure; a new neurologic deficit; or a new onset of seizures. Migraine in children with NF1 can usually be managed in the same way as similar headaches in the general population and may include lifestyle modification, the use of non-prescription medication and, in some cases, treatment with prescription medications.

The guidelines also mention that seizures are more common in people with NF1 than in the general population. This may be due, in part, to structural or vascular changes in the brains of people with NF1, and rarely indicate the presence of a tumor. The guidelines recommend brain MRI at the initial onset of seizure in those with NF1 and management by a physician who is experienced in the treatment of seizures.