Plexiform neurofibromas are a type of benign tumor that develops along nerve bundles. These growths are commonly associated with Neurofibromatosis Type 1 (NF1), a genetic disorder. While not cancerous, these tumors can grow considerably and infiltrate surrounding tissues, potentially leading to significant health issues depending on their location. They are believed to be present at birth in many individuals with NF1.
Understanding Plexiform Neurofibromas
Plexiform neurofibromas are characterized by their diffuse, infiltrative growth pattern, involving multiple nerve fascicles and extending along the length of nerves and their branches. Unlike cutaneous neurofibromas, which are smaller and located on or just under the skin surface, plexiform neurofibromas are often deeper and can affect vital structures. They can feel like a “bag of worms” or a mass of thickened nerves under the skin when palpable.
The cause of plexiform neurofibromas is a mutation in the NF1 gene. This gene produces neurofibromin, a protein that acts as a tumor suppressor by regulating cell growth. When the NF1 gene is mutated, neurofibromin function is impaired, leading to uncontrolled cell proliferation and tumor formation. Schwann cells are a primary component of these tumors.
Plexiform neurofibromas are composed of various cell types, including Schwann cells, fibroblasts, and mast cells. Mast cells are thought to contribute to the tumor microenvironment and promote growth. These tumors can occur anywhere in the peripheral nervous system and are a distinct feature of NF1, affecting approximately 30% to 50% of individuals with the condition.
Recognizing the Signs and Impact
The manifestations of plexiform neurofibromas vary widely, depending largely on their location and size. Superficial tumors may present as a visible or palpable mass beneath the skin, sometimes accompanied by skin changes like thickening, hyperpigmentation, or increased hair growth over the affected area. Deeper tumors, however, may not be externally visible and are often discovered due to symptoms or imaging findings.
Common signs and symptoms include pain, numbness, or weakness resulting from the tumor compressing nerves or surrounding tissues. If a tumor affects the face or head, it can lead to disfigurement and may press on the brain, causing headaches. Tumors near sensory organs can impair vision or hearing.
Plexiform neurofibromas can also lead to bone deformities, such as scoliosis or bowing of long bones. Tumors in the abdomen can involve the intestinal or bladder walls, potentially causing dysfunction. These tumors can significantly affect a person’s daily life, function, and quality of life. Diagnosis often involves a physical examination followed by imaging techniques such as Magnetic Resonance Imaging (MRI), which is the standard for evaluating neural tissues.
Management and Treatment Approaches
Managing plexiform neurofibromas often involves a multidisciplinary approach tailored to the individual’s specific needs. Surgical intervention is a primary treatment option, particularly for symptomatic tumors or those affecting important structures like the airway or spine. However, complete surgical removal of plexiform neurofibromas is frequently challenging due to their infiltrative nature, involvement of multiple nerve branches, and often complex vascular systems, which can lead to significant bleeding and potential nerve damage.
Because complete removal is often not feasible, a “debulking” procedure may be performed, where a portion of the tumor is removed to alleviate pressure or improve cosmetic appearance. Despite surgery, plexiform neurofibromas can regrow. This has led to the development of targeted therapies to manage tumor growth.
One significant advance is the use of MEK inhibitors, a class of targeted medications. Selumetinib (Koselugo) is an FDA-approved MEK inhibitor for children aged two and older with NF1 who have symptomatic, inoperable plexiform neurofibromas. This medication works by blocking proteins that are often overactive in NF1 and promote tumor growth. Clinical trials have shown that selumetinib can reduce tumor volume in a significant percentage of patients, with some experiencing improvement in associated pain and complications.
Risk of Malignant Transformation
While plexiform neurofibromas are benign tumors, they carry a lifetime risk of transforming into malignant peripheral nerve sheath tumors (MPNSTs). This transformation is a serious complication of NF1, with an estimated lifetime risk ranging from 8% to 13% for individuals with the condition. MPNSTs are aggressive cancers that can arise from pre-existing plexiform neurofibromas.
Signs that may suggest a malignant change include rapid growth of a pre-existing tumor, new or worsening pain that might even wake an individual from sleep, or the development of new neurological deficits such as weakness or numbness. Certain imaging features can also indicate malignant transformation. Vigilance and regular monitoring, often through imaging studies, are important for individuals with plexiform neurofibromas to detect any potential malignant changes early.