Secondary Vascular Alterations in Diffuse and Plexiform Neurofibroma

Abstract

The purpose of this report is to illustrate a change affecting the peripheral vessels of some patients with neurofibromatosis type I (NF-1), which, although not particularly rare and sometimes striking in its morphologic appearance, is very rarely mentioned in standard surgical pathology textbooks or in articles dealing with the pathology of neurofibromatosis. As a matter of fact, practically all the scanty accounts that have been written on the subject have been published in clinical or surgical journals. As a consequence, many pathologists are unaware of this abnormality and fail to recognize its real nature when encountering it. We recently observed a typical case of this occurrence in a 24-year-old man with multiple cafe-au-lait spots and a past history of removal of a neurofibroma of the left hand 5 years previously. He now presented with a mass involving the skin, subcutaneous tissue, and fascia in the right calf, which has been slowly growing for the past 2 years to reach a size of 18 cm. The differential diagnosis on imaging studies included scleroderma/morphea, an inflammatory lesion, and a neoplastic condition. The hematoxylin and eosin–stained sections showed a hypocellular lesion composed of widely spaced cells with ovoid to thin elongated nuclei and scanty cytoplasm embedded in a mucopolysaccharide-rich, variably collagenous matrix. The tumor was unencapsulated and ill defined, spreading extensively along connective tissue septa and between adipocytes. Despite its infiltrative growth, it did not destroy the normal structures it encompassed but rather enveloped them gently and, in addition, there were areas of plexiform neurofibroma. The features were typical of diffuse and plexiform neurofibroma, a diagnosis supported by the strong immunoreactivity of the tumor cells for S-100 protein. The history of an antecedent neurofibroma and the fact that the current lesion was of the diffuse neurofibroma type were consistent with the interpretation that the patient suffered from NF-1. The most interesting pathologic changes present in the current soft tissue tumor were seen in the mediumand large-sized vessels situated within the lesion. They affected predominantly the arteries, and were mainly characterized by (a) a focally prominent subendothelial thickening resulting from the accumulation of a highly myxoid hypocellular tissue, sometimes resulting in significant stenosis and accompanied by a scattering of S-100 protein-negative fibroblasts; (2) A hypercellular proliferation of S-100 protein-positive spindle cells consistent with peripheral nerve sheath cells encircling the vessels, in the area normally occupied by the vasa vasoru (Figures 1-4). The term NF-1 vasculopathy has been coined in the medical literature as a generic designation encompassing a variety of vascular changes that have been described in NF-1 patients, including aneurysms, stenosis, arteriovenous malformations, and vascular compression. These lesions have been extensively studied from a clinical 436556 IJSXXX10.1177/1066896912436556Pirola and OliffInternational Journal of Surgical Pathology