Malignant Peripheral Nerve Sheath Tumor
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1 C H A P T E R 120 Malignant Peripheral Nerve Sheath Tumor Currently, malignant peripheral nerve sheath tumor (MPNST) is the most commonly used generic name for the neoplasms known in the past as neurosarcoma, neurogenic sarcoma, neurofibrosarcoma, or malignant schwannoma. 1 6 CLINICAL FEATURES MPNST is a rare neoplasm, representing only 2% of all peripheral nerve sheath neoplasms. 7 Most cases originate by malignant transformation of a preexisting neurofibroma in patients with von Recklinghausen neurofibromatosis. 8 Plexiform neurofibroma is the clinicopathologic variant of neurofibroma with the highest potential to transform into MPNST. MPNST lesions that affect the skin only rarely originate in the dermis or upper parts of the subcutis, 9,10 and in most cases, cutaneous involvement is due to an extension of a malignant tumor located in deep soft tissues 11 (Fig ). Superficial MPNST have a better prognosis than deep lesions. 12 In most cases, MPNST neoplastic cells show differentiation toward Schwann cells, although a rare variant of MPNST with differentiation toward perineurial cells has recently been described MPNST mostly originates in the subcutaneous soft tissues of the limbs in young adult patients with von Recklinghausen neurofibromatosis Usually, the precursor tumor is a plexiform neurofibroma that had remained asymptomatic and stable for years and then began to be painful and to grow rapidly. The frequency with which an MPNST originates out of a plexiform neurofibroma in a patient with von Recklinghausen neurofibromatosis is estimated to be between 8% and 12%, while in the general population, the frequency is %. 18,19 In some cases, there is a history of previous radiation therapy of a preexisting plexiform neurofibroma, 20 but on most occasions, there is no apparent triggering factor. In most large series, the incidence of MPNST in both genders varies with the type of patients studied. When patients with neurofibromatosis type 1 are included, MPNST is more frequent in males, while tumor incidence is similar in both genders when only sporadic cases are analyzed. MPNST only very rarely ulcerates the overlying epidermis. Most patients complain of undefined pain or neurologic motor and/or sensory FIGURE Clinical features of an MPNST on the right arm of an 11-year-old girl with von Recklinghausen disease. Besides the subcutaneous mass in the arm, numerous café-au-lait spots are seen. deficiencies in the region innervated by the affected nerve, including paresthesia, loss of deep tendinous reflexes, muscle weakness, or tingling or sensation of numbness. Sometimes these symptoms only appear when the affected nerve is pressed. 19 Most MPNST lesions arise in proximal areas of the lower limbs, primarily affecting large nerve trunks, including the sciatic, medial, or external tibial nerve or the vertebral nerves but rarely involving cervical or lumbar nerves. In general, MPNST in patients with von Recklinghausen neurofibromatosis occurs preferentially along the central axis of the body, while MPNST outside the setting of neurofibromatosis prefers a more peripheral topography. 21 The prognosis of MPNST is dismal with a mean survival of 2 to 3 years postdiagnosis
2 788 SECTION 4 NEURAL TUMORS HISTOPATHOLOGIC CHARACTERISTICS At low magnification, MPNST presents as an ill-defined neoplasm that deeply infiltrates subcutaneous fat and adjacent soft tissues. Conventional histopathology without the aid of immunophenotyping often does not allow differentiating MPNST from other soft tissue sarcomas; therefore, obvious contiguity of the neoplasm with a nerve trunk is one of the most useful clues to the diagnosis of MPNST. The tumor consists of fascicles of spindle cells arranged in an undulated, disorganized, or interwoven pattern; large necrotic areas are usually seen throughout the tumor 23 (Fig ). Some lesions alternate highly cellular areas with less cellular and more myxoid ones. 24 Neoplastic cells have a large, fusiform, hyperchromatic, and pleomorphic nucleus (Fig ). Focally, a palisading arrangement of these nuclei can be encountered as expression of an attempt to form rudimentary Verocay bodies. Occasionally, areas occur in which the neoplastic cells are arranged forming perivascular swirls or pseudorosettes around hyaline collagen bundles. Other unusual histopathologic findings are the replacement of preexisting nerves by aggregates of neoplastic cells and the presence of tumor islets that seem to protrude into vascular lumina. Sometimes obvious contiguity exists between a preexisting plexiform or atypical neurofibroma and a gradually transforming MPNST. 25 The presence of melanin pigment in the cytoplasm of MPNST neoplastic cells is a rare finding. In the only reported case, the lesion did not contain psammoma bodies and the patient did not present with Carney complex. 26 In general, tumors with the highest cellularity and with a high mitotic index show the most aggressive biologic behavior. A plexiform variant of MPNST has been reported that seems to be particularly frequent in the limbs of children and adolescents and to have a better prognosis than most FIGURE Histopathologic characteristics of plexiform MPNST. A: Panoramic view showing a poorly-demarcated subcutaneous neoplasm with large necrotic areas. B: The neoplasm is highly cellular and consists mostly of spindle cells. C: The neoplastic cells display pleomorphic nuclei with numerous mitotic figures, many of which are atypical. D: Detailed image of the cytologic features of the neoplastic cells and an atypical mitotic figure.
3 CHAPTER 120 MALIGNANT PERIPHERAL NERVE SHEATH TUMOR 789 FIGURE Histopathologic characteristics of a plexiform MPNST. A: Panoramic view showing a poorly circumscribed tumor. B: The neoplasm is very cellular. C: Neoplastic cells are fusiform with hyperchromatic and pleomorphic nuclei. D: Numerous atypical mitotic figures. MPNST forms. This lesion frequently recurs locally but has a very low metastatic potential. 27 Low magnification shows that the lesion is not encapsulated and consists of spindle cell fascicles arranged in a disorganized or in a plexiform pattern throughout the entire dermis, extending into the subcutaneous fat (Fig ). Each individual fascicle consists of spindle cells with oval, occasionally undulated, hyperchromatic, and monomorphic nuclei. At high magnification, few mitoses can be seen, a mean of 4 mitoses per 10 high power fields. 27 In some areas, spindle cell nuclei tend to arrange in palisades within the fascicles. In other areas, the nuclei are arranged in semicircles mimicking rudimentary Verocay bodies. In deeper areas, the lesion is less cellular and nests of spindle and oval cells are seen embedded in a myxoid stroma. Sometimes, in deeper areas of the lesion, there are very thick abnormal nerve trunks that may blend with the spindle cell fascicles. Some epithelioid variants of MPNST have been reported in which the nodular tumor cell aggregates consist of large, round cells with a large eosinophilic cytoplasm, vesicular nucleus, and prominent nucleolus; these nodules are surrounded by connective tissue fibers (Fig ). Occasionally, multinucleated cells are seen within the epithelioid cell nodules, and mitotic figures are not uncommon, many of which are atypical. Some authors have postulated that these epithelioid variants of MPNST evolve from benign epithelioid cell schwannomas 33 and have a better prognosis than do other MPNSTs, 28,30 although the limited number of described cases of this epithelioid variant of MPNST does not allow extrapolating prognostic data. Tumor variants of MPNST with divergent differentiation have also been reported; these show conspicuous areas of osteogenic sarcoma, chondrosarcoma (Fig ), angiosarcoma, rhabdomyosarcoma, or epithelial glandular elements throughout an MPNST with predominant Schwann cell differentiation. 35,38 53 Some authors use the term malignant mesenchymoma 26 as a generic name for MPNST with divergent differentiation. MPNST with rhabdomyoblastic differentiation is also known as
4 790 SECTION 4 NEURAL TUMORS FIGURE Plexiform MPNST. A: At low magnification, the lesion is not encapsulated and consists of spindle cell fascicles distributed in a disorganized manner within the entire dermis and extending into the subcutaneous fat. B: Each individual fascicle is sharply circumscribed. C: Each fascicle consists of spindle cells, each with an oval nucleus, which occasionally is undulated, hyperchromatic, and monomorphous. D: At high magnification, rare mitoses are seen. E: In deeper areas, the lesion is less cellular. F: In these deeper areas, nests of fusiform cells are embedded in a myxoid stroma.
5 CHAPTER 120 MALIGNANT PERIPHERAL NERVE SHEATH TUMOR 791 FIGURE cont. G: A hypocellular fascicle is surrounded by myxoid stroma. H: Cytologic features of the neoplastic cells at high magnification. FIGURE Histopathologic characteristics of epithelioid MPNST. A: Panoramic view showing an infiltrating neoplasm with a sheet-like pattern. B: Neoplastic cell aggregates consist of large, round cells. C: Neoplastic cells display a large eosinophilic cytoplasm, a vesicular nucleus, and a prominent nucleolus. D: Mitotic figures, many of which are atypical, may be seen among the neoplastic cells.
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