Neurofibromas in NF1 patients have an increased tendency to occur near the spinal cord and the brain and in uncommon locations such as the tongue and parotid glands. In contrast, sporadic neurofibroma is a tumor of the periphery of the peripheral nervous system and occurs most commonly in the extremities.
Neurofibromas are benign tumors and the tumor cells have features of Schwann cells, perineural cells, and fibroblast. There are three major types of neurofibromas:
cutaneous neurofibromas
subcutaneous neurofibromas
plexiform neurofibromas.
NF1-associated plexiform neurofibroma
Plexiform neurofibroma is the least common. Plexiform neurofibromas occur almost exclusively in patients with NF1 and they are often multiple. Many of them occur in a superficial location but they can also occur in deep locations.
Grossly, a typical, small to medium sized tumor appears as a spindle shaped enlargement with the head and tail merging with the surrounding tissue or the nerve trunks that they arise from. In well preserved surgical specimens that are removed en bloc, plexiform neurofibroma appears as a tangle of enlarged nerve trunks reminiscent of a piece of curled up noodle or “a bag of worms”.
On cut section, the individual enlarged nerve trunks may appear as segregated individual bundles. A myxoid appearance is also characteristic.
Although the tumors tend to confine their involvement in large nerves to the nerve trunks themselves, their diffuse involvement along the length of the nerve makes complete resection difficult if not impossible. In contrast, sporadic neurofibromas are sharply circumscribed.
Microscopically, plexiform neurofibroma shares common features with other neurofibromas. In essence, the tumor has a hypocellular, myxomatous background of variable degree. Fine collagen fibers are also present at a variable density.
The proportion of collagenous to myxomatous component is highly variable. There are widespread spindle cells with ovoid to thin and elongated, bland nuclei with minimal or no pleomorphism and without prominent nucleoli. The neoplastic tissue typically fills and expands the nerve trunk.
In contrast to schwannoma where residual nerve trunk may be identified at the periphery, the nerve trunk is diffusely involved and expanded and no residual nerve trunk can be demonstrated. Mitosis, high cellularity, necrosis and high grade pleomorphism should not be present.
Demonstration of these features would raise a strong suspicion for malignant transformation which is not an uncommon event in NF1 patients.
Immunochemistry
Immunohistochemically, the spindle cells are positive for S-100 protein. Entrapped axons can also be demonstrated by immunohistochemistry for neurofilament proteins.
In general, the morphologic features of plexiform neurofibroma are highly characteristic and do not require immunohistochemistry for diagnostic purposes.
See also