Plexiform neurofibromas are benign tumors that develop in individuals with Neurofibromatosis Type 1 (NF1). Unlike other neurofibromas, they grow extensively along nerve pathways, often causing significant symptoms due to their diffuse nature. This article covers their characteristics, genetic origins, diagnosis, and treatment.
Understanding Neurofibromas
Neurofibromas are benign tumors originating from the protective sheaths surrounding nerves, specifically Schwann cells. They can form along any peripheral nerve, from just under the skin to deeper nerves within organs or along the spine. While many are small and cause minimal issues, their presence is often associated with neurofibromatosis.
They are composed of an overgrowth of nerve tissue, including Schwann cells, fibroblasts, and other supporting cells. These nerve sheath tumors can appear as soft bumps on or under the skin. Their size and location determine whether they cause symptoms.
Characteristics of Plexiform Neurofibromas
Plexiform neurofibromas differ from other neurofibroma types by their diffuse, infiltrative growth pattern. They involve multiple nerve bundles (plexuses) and can spread extensively along nerve pathways and into surrounding tissues. They often feel like a “bag of worms” under the skin due to their intertwined nerve fascicles.
These tumors can reach considerable sizes and are often present at birth, though they may not become clinically apparent until early childhood (ages 3-5 years). Their growth can be rapid in younger children, potentially increasing in volume by 20% to 240% per year. While benign, plexiform neurofibromas carry an increased risk (8% to 15%) of transforming into malignant peripheral nerve sheath tumors (MPNSTs).
Genetic Basis and Development
Plexiform neurofibromas are linked to Neurofibromatosis Type 1 (NF1), a genetic disorder. NF1 results from a mutation in the NF1 gene on chromosome 17. This gene provides instructions for neurofibromin, a protein that acts as a tumor suppressor.
Neurofibromin regulates cell growth and division by managing the Ras protein. When the NF1 gene mutates, it leads to non-functional or absent neurofibromin, causing uncontrolled Schwann cell growth. This deregulation of the Ras signaling pathway contributes to plexiform neurofibroma formation. These tumors originate from the Schwann cell lineage, with NF1 function loss in these cells initiating their development.
Clinical Presentation and Diagnosis
The manifestation of plexiform neurofibromas varies widely depending on their size and location. They can appear as visible lumps beneath the skin, causing disfigurement, particularly if on the face or neck. Deeper tumors may not be apparent but can cause symptoms by compressing nerves or organs. Common symptoms include pain, tingling, numbness, weakness, and functional impairment.
Diagnosis begins with a physical examination, where a doctor feels for soft masses. Imaging techniques are essential for confirming the diagnosis and assessing tumor extent. Magnetic Resonance Imaging (MRI) is the primary imaging method, precisely locating tumors, delineating borders, and evaluating involvement with surrounding tissues. A biopsy may be performed to confirm diagnosis or rule out malignant transformation, especially with rapid growth or new symptoms.
Treatment Approaches
Managing plexiform neurofibromas requires an individualized approach, considering the tumor’s size, location, and symptoms. Surgical removal is a common strategy, especially for accessible tumors causing significant symptoms or disfigurement. Complete removal is challenging due to the tumor’s infiltrative nature and close association with nerves and blood vessels, often leading to partial removal (debulking) to alleviate symptoms.
Medical therapies have emerged as important options, particularly for inoperable tumors. MEK inhibitors, such as selumetinib (Koselugo), are approved for children with NF1 and symptomatic, inoperable plexiform neurofibromas. These medications block signals contributing to tumor growth, reducing tumor volume and improving symptoms for some patients. Management involves a multidisciplinary team of specialists to optimize patient care.