Neurofibromas are noncancerous growths that develop along nerves in the body, primarily arising from the cells that form the protective covering of peripheral nerves (Schwann cells). The development of these tumors is linked to a functional loss in the neurofibromin protein, a tumor suppressor. Neurofibromas are the defining feature of neurofibromatosis type 1 (NF1), a common genetic disorder affecting the nervous system and skin. While they can occur as solitary lesions, the presence of multiple neurofibromas is typically associated with NF1.
The Earliest Physical Manifestations of Neurofibromas
The first appearance of a neurofibroma varies depending on whether the growth is on the skin surface (cutaneous) or positioned deeper underneath. Most cutaneous or dermal neurofibromas typically begin to manifest around the onset of puberty. These initial tumors are often very small, frequently described as being no larger than a pea or a small papule. They usually present as dome-shaped bumps that are soft and sometimes fleshy to the touch.
The color of these lesions is usually similar to the surrounding skin, or they may appear slightly pink, purplish, or hyperpigmented. A unique characteristic is that some small dermal neurofibromas can be pushed inward, or “buttonholed,” when gentle pressure is applied. The texture can range from soft and rubbery to slightly firmer. While they can appear anywhere on the body, they frequently emerge along the trunk and extremities.
Subcutaneous neurofibromas develop deeper, situated just beneath the surface of the skin. At first, these are felt rather than seen, presenting as small, firm nodules when palpated. Because they are rooted around a deeper nerve, these initial growths can sometimes cause localized tenderness or a tingling sensation when pressed.
Plexiform neurofibromas involve multiple bundles of nerves and are often congenital or detected in early childhood. These growths can be felt as a soft mass under the skin, sometimes presenting with an overlying patch of darker or thickened skin. Unlike the small, discrete tumors, plexiform neurofibromas involve a larger, more diffuse area, sometimes leading to subtle bulging or distortion of the affected region.
Key Associated Skin Markers
While neurofibromas are growths, the earliest and most common physical indicators of neurofibromatosis type 1 are flat pigment changes on the skin. These include Café-au-lait macules (CALs), which are flat, light brown or tan patches resembling coffee with milk. These macules may be present at birth or develop during the first few years of life, typically having smooth or slightly irregular borders.
The presence of a few CALs is common in the general population and is not a cause for concern. However, multiple CALs that meet specific size criteria are a strong clinical sign associated with NF1. Specifically, six or more spots measuring over five millimeters in children before puberty or over 15 millimeters in adults are required for diagnosis.
Another characteristic early skin sign is axillary or inguinal freckling, sometimes called Crowe’s sign. This involves the appearance of numerous small, distinct, reddish-brown freckles clustered in the armpits or groin area. These freckles are smaller and more numerous than typical sun-induced freckles and typically emerge in childhood, often between three and five years of age.
CALs and axillary freckling serve as early alerts, sometimes appearing years before neurofibromas begin to develop in adolescence. The combination of these specific, patterned skin changes helps clinicians form a diagnosis.
How Early Neurofibromas Change Over Time
Once they first appear, neurofibromas generally follow a pattern of slow, progressive development throughout a person’s lifespan. Cutaneous neurofibromas typically increase in both number and size as an individual ages. Periods of accelerated growth often correspond to hormonal changes, such as puberty and pregnancy, when existing neurofibromas may enlarge or new ones may emerge more frequently.
The long-term progression means that a person with NF1 may eventually develop anywhere from a few to hundreds of these tumors. Over time, some dermal neurofibromas may lose their dome shape and become pendulous, appearing to hang from the skin on a small stalk. The texture can also change, with some lesions becoming softer and more gelatinous.
Plexiform neurofibromas, which can be present at birth, often exhibit their most rapid growth during early childhood, specifically before the age of five. Although their growth rate slows significantly after this period, they can continue to gradually expand throughout life. The continued growth of these deeper tumors can cause complications by impinging on surrounding nerves, organs, or bones.
A small fraction of plexiform neurofibromas carry a lifetime risk of transforming into a malignant peripheral nerve sheath tumor (MPNST). This transformation is suspected when a previously stable lesion begins to grow very rapidly, becomes noticeably harder, or causes new, persistent pain. For the majority of cutaneous and subcutaneous neurofibromas, the growth pattern remains benign, with changes mainly affecting appearance or comfort.
When to Seek Professional Medical Evaluation
Any new, persistent, or changing growth on or under the skin warrants a professional medical evaluation, particularly if there is a family history of neurofibromatosis. Consulting a dermatologist or a specialist familiar with NF is important for an accurate assessment and definitive diagnosis. A medical professional can distinguish a neurofibroma from other common skin lesions and evaluate it in the context of other markers.
The presence of six or more Café-au-lait macules that meet the specific size criteria, or the finding of axillary or inguinal freckling, is a strong indication that professional assessment is necessary. Only a physician can use the complete set of diagnostic criteria to confirm a condition like NF1.
Specific changes in an existing neurofibroma should trigger a prompt medical appointment to rule out rare complications. These worrisome signs include:
- Any sudden, rapid increase in the size of a lesion.
- The onset of new or increasing pain that lasts for more than a month.
- A change in the tumor’s texture from soft to firm or hard.
- New neurological symptoms, such as unexplained weakness or numbness in a limb.
Ongoing, regular monitoring by a multidisciplinary care team is recommended for individuals diagnosed with NF1. Annual checkups should include a comprehensive skin and neurological examination to track the progression of existing lesions and detect any new developments early. Early detection allows for timely intervention and better long-term management.