Because the occurrence of tumors is one of the hallmarks of all forms of NF, imaging studies, such as CT or MRI scans, serve a central role in the clinical diagnosis and management of the disease. This month, I’d like to focus our discussion on the primary clinical approaches regarding the use of imaging in the diagnosis and management of NF. Within the NF clinical community, there are essentially two different perspectives on the use of imaging. The first approach advocates proactive screening to identify the presence of tumors. While many of these tumors may be small at the time, the idea is that early identification of the tumors may allow for more effective treatment. The second approach recommends the use of imaging only when specific clinical indications are present. I have tended to adhere to the latter approach of performing imaging to address specific clinical problems or concerns.

Clinical Approach to Imaging

Although lesions can be identified at an early point in some people, the problem is that most are untreatable at that point in time. Moreover, in some cases, identifying these tumors at an early stage may open the possibility of instituting potentially harmful treatments, including surgery. Finding these tumors can also cause anxiety and worry in many patients and families. For these reasons, we in the UAB NF Clinic advocate a clinical approach to imaging based on the presence of specific signs, symptoms, or problems.

A common goal of imaging in NF is to identify tumors in the nervous system, especially, in children, the presence of an optic glioma, which is a tumor of the optic pathway that occurs in 15% of children with NF1. While this condition can cause problems such as loss of vision or hormonal imbalances, it is known that the majority of optic gliomas are non-progressive and do not require treatment. An important question for clinicians is how to identify those patients with optic gliomas who need treatment. We have tended to use the clinical measures to identify children at risk for optic glioma, including routine yearly eye exams with a pediatric ophthalmologist. If a concern arises based on the ophthalmologic exam, a brain MRI scan would be performed. We would plan to re-evaluate this approach in the future when treatments have advanced to the point that early scanning for the identification of optic glioma tumors is beneficial. For example, if scanning children at a certain age could identify optic gliomas for a specific treatment protocol, preventive scanning could be justified. However, at this time, the information gained from preventive scanning for optic gliomas does not offset the risks, such as the fact that sedation is required for imaging in children and there is no definite clinical benefit to identifying these tumors in the absence of clinical symptoms.

The use of whole body MRI is beginning to emerge as a screening tool for the identification of tumors in people with NF. This approach can identify tumors, but the detail of imaging is usually less than would be obtained from a focused study. As with brain imaging, the question is what would we do with the information if we found a tumor that currently can’t be treated? As treatment options mature, we may reach a point where identifying tumors early on is beneficial to institute therapy. For the moment, however, routine imaging produces a fair amount of information that is not actionable as well as the risk of anxiety in patients and their families. For these reasons, we continue to take a clinical approach to imaging that involves performing imaging studies when clinically indicated, though not as a broad screening test.

A few months ago, I reviewed a publication of clinical guidelines for adults with NF1. Recently, a parallel set of guidelines for children with NF1 was published. I will review these guidelines as well, beginning with next month’s blog.

Questions From Individuals Outside the NF Clinic

In this month’s post, I’d like to explain a new method I’ve established for responding to the many emails I receive from individuals from all over the world with medical questions about their children whom I have not seen clinically.  Most of these email questions are from parents who are concerned that skin pigmentation on their children might be café-au-lait spots that can be indicative of NF. These emails are often accompanied by photos of the skin spots, which very often are not of high enough quality to clearly see the spots. In the past, I have tried to answer these emails in a general way as best as possible, although an email exchange allows for only limited information to be shared. 

I certainly understand that parents often experience anxiety related to these questions and that many people live in areas where a clinician with experience in NF is not available. Also, there often are long wait times to get into a specialty clinic.  While I empathize with these parents’ concerns and need for guidance, it isn’t possible for me to provide medical advice to someone whom I have not seen clinically. When I perform a clinical evaluation of a child with café-au-lait spots, I include a comprehensive physical exam as well as a medical and family history.  As such, my clinical impressions are based on much more information than can be provided in an email exchange.

As a way to provide concerned parents with general information that might be helpful, I’ve written a brief statement about NF and café-au-lait spots that I will now forward to individuals who send me email questions about skin pigmentation and other NF-related concerns. Although I’m unable to reply to these questions with specific information, I’m hoping that the statement I’ve prepared will provide helpful information and initial guidance. If I receive frequently asked questions that aren’t addressed in the statement, I can always include additional information in the statement as well as provide these updates in a future NF blog. 

Questions from Physicians and NF Clinic Patients

Because we have an established and well-known NF Clinic, I often also receive email questions from physicians regarding their patients, which I do my best to answer. In this situation, I’m not providing medical advice, and the contacting physician is taking responsibility for providing care to the patient. In these situations, we also often review imaging or other test results submitted by physicians seeking guidance for their patients.

For patients with whom we already have an established clinical relationship, we’re glad to answer questions. Because email is not the preferred communication method due to privacy and security concerns, we encourage our patients to either call the NF Clinic or use the UAB Patient Portal, which we check regularly. The patient portal is a secure and efficient way for patients to ask questions or request and appointment, and we encourage all of our patients to register for the portal as a way to enhance and facilitate communication with the NF Clinic.  Any who need help in registering can call the clinic for assistance.

As I discussed in last month’s blog, the UAB NF Clinic staff is making the necessary adjustments to accommodate all patients after Dr. Lane Rutledge’s unexpected passing at the beginning of the year.  Our nurse practitioner, Ms. Tammi Skelton, who works with me in the NF Clinic and had also worked with Dr. Rutledge in clinic, is assisting Dr. Rutledge’s former patients with immediate needs in scheduling appointments with me as needed. Also, we have plans to open an extra clinic session once a week with the help of pediatric neuro-oncologist Katie Metrock, M.D. With all of us working together, we can continue providing the same high level of care to all of Dr. Rutledge’s former patients in the NF Clinic. We are also working with the adult neuro-oncology service to integrate experts in this area into the care of adults with NF.

Differences in Schwannomas and Neurofibromas

Because we frequently receive questions about the difference between neurofibromas and schwannomas, I’d like to explain the distinctions between these types of tumors.  Both neurofibromas and schwannomas are tumors of the peripheral nerve sheath, and the primary tumor cell in both is the Schwann cell.  There is, however, a difference in how the cells that comprise schwannomas and neurofibromas behave.  In schwannomas, the Schwann cells grow as a mass that pushes the nerve aside and may compress the nerve.  Also, the majority of cells in the schwannoma are Schwann cells.  In contrast, neurofibromas include a variety of cell types, including Schwann cells, but also others, such as specific types of blood cells, connective tissue cells, and other cells from the nerve sheath.  Neurofibromas usually consist of a loose mixture of these various cell types surrounding the nerve, but not displacing it.  They can compress the nerve, particularly if there is a nearby rigid structure, such as a bone.  These distinctions are mainly visible to the pathologist, who would examine a sample of a tumor through the microscope. 

Neurofibromas can sometimes be distinguished from schwannomas by their imaging characteristics, but this distinction is more difficult and sometimes not possible to do definitively.  Because of this, some people have been told that they have either neurofibromas or schwannomas based on imaging, but in fact the tumor has been mis-identified.  The distinction is important, however, in terms of both underlying diagnosis and treatment.  Neurofibromas are characteristic of NF1, whereas schwannomas are typically seen in NF2 and schwannomatosis.  There is some scientific debate as to whether neurofibromas are ever seen in NF2 or schwannomas in NF1.  Whatever the answer, it is a good rule of thumb that neurofibromas go with NF1 and schwannomas with NF2.  Usually, if a person with NF1 is told he or she has a schwannoma, or a person with NF2 is told he or she has a neurofibroma, it will turn out that the terminology of the two tumors was used incorrectly.  We have also heard from some people that they were told that they have both NF1 and NF2.  Although theoretically possible based on having two independent genetic mutations, this would be extraordinarily rare; an error in diagnosis is much more common.

It should be remembered, however, that it is possible for a person with NF1 to develop a vestibular schwannoma that is also a hallmark feature of NF2, on one or both hearing nerves.  Vestibular schwannomas are relatively common in the general population, and individuals with NF1 can coincidentally develop vestibular schwannomas without having NF2.  Vestibular schwannomas in the general population usually occur later in life than they do in NF2, so the sporadic vestibular tumors in rare individuals with NF1 usually happen later in life as well.

The distinction between NF1, NF2, and schwannomatosis is important to establish for clinical follow-up.  The surveillance and treatment guidelines are quite different for the three conditions.  That is why, when we see a new patient, we try to review a comprehensive picture, including medical history, review of any pathology and genetic testing, physical exam, and family history.  This facilitates correct diagnosis and provides guidance for further management.