Malignant peripheral nerve sheath tumor with perineurial differentiation: "malignant perineurioma"

Although benign tumors derived from the nerve sheath perineurial cell have been described from a variety of anatomic sites and are known to be a component of a number of benign neoplasms, malignant nerve sheath tumors of perineurial origin are exceedingly uncommon.

We report an unusual case of a 70-year-old male who presented with a rapidly growing mass of the left arm, subsequently shown to be a malignant nerve sheath tumor with perineurial differentiation. A brief microscopic differential diagnosis and review of the literature are discussed.

Histologic sections show a partially circumscribed tumor of atypical spindle cells arranged in sweeping fascicles embedded in a myxoid matrix with focal whorling. Nuclear pleomorphism was evident among scattered typical and atypical mitotic figures (mean mitotic index of 7/10 high-power fields). The immunophenotypic profile consisted of only vimentin and epithelial membrane antigen (EMA) positivity, while antibodies to S-100, CD34, smooth muscle actin, and pankeratins were negative. Ultrastructural features included spindle cells with long cytoplasmic processes invested by interrupted basal lamina and pinocytotic vesicles, consistent with perineurial differentiation.

While the histogenic source of the benign perineurioma, the perineurial cell has only rarely been described in conjunction with malignant tumors. All cases to date have shown EMA-positive and S-100-negative atypical spindled cells arranged in fascicles embedded in a myxoid matrix. In addition to immunohistochemistry, ultrastructural examination may be necessary to support the diagnosis. The diagnostic differential includes melanoma, spindle cell squamous cell carcinoma, atypical fibroxanthoma, leiomyosarcoma, and conventional malignant peripheral nerve sheath tumor, most commonly of Schwannian differentiation. Recognizing perineurial differentiation is important since few cases have been reported to date and the biological potential of these neoplasms is not known.