DOI: 10.1148/rg.233025153
(Radiographics. 2003;23:790-794.)
© RSNA, 2003
Malignant Peripheral Nerve Sheath Tumor1
Peter A. Hrehorovich, MD,
Hubert R. Franke, MD,
Suresh Maximin, MD and
Paula Caracta, MD
1 From the Departments of Radiology (P.A.H., H.R.F., S.M.) and Pathology (P.C.), St Vincent’s Catholic Medical Center, 355 Bard Ave, Staten Island, NY 10310. Received October 15, 2002; revision requested November 25 and received December 10; accepted December 16. Address correspondence to P.A.H. (e-mail: phrehorovich@yahoo.com).
Index Terms: Nerves, neoplasms, **.3252 • Nervous system, neoplasms, **.325 • Neurofibromatosis, **.1831
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History
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A 35-year-old black man was admitted for management of increasing abdominal distention. His medical history included type 1 neurofibromatosis (NF1), also known as von Recklinghausen disease. Five weeks prior to admission, he was hospitalized because of diffuse abdominal pain. Computed tomography (CT) with subsequent image-guided biopsy revealed an intraabdominal mass, which was identified as consistent with a malignant peripheral nerve sheath tumor (MPNST). At laparotomy, the mass measured 10 x 9 x 8 cm and encased the aorta and inferior vena cava. It was debulked, since full excision was not possible. Repeat imaging studies showed rapid growth.
At the time of the current admission, physical examination revealed several café-au-lait spots, multiple cutaneous neurofibromas over the entire body, and a solid midline mass of about 15 x 20 cm in transverse and vertical dimensions, respectively. He had a hematocrit of 24%, white blood cell count of 14.2 x 103/µL, and albumin level of1.8 g/dL. The remaining results of routine laboratory tests were unremarkable. Radiation therapy was begun during the second hospital admission. On the ninth hospital day, the patient became lethargic and required endotracheal intubation and ventilatory assistance. His clinical status continued to decline, and he died on the 15th hospital day.
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Imaging Findings
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An abdominal and pelvic CT study with intravenous and oral contrast material was performed. It demonstrated a large, heterogeneous, solid mass in the mid–abdominopelvic region that measured approximately 12 x 8 x 10 cm and encased the abdominal aorta just proximal to the bifurcation as well as the common iliac arteries bilaterally (Fig 1a). There was no evidence of bowel or ureteral obstruction. Numerous low-attenuation, lobular lesions were noted in the thoracic and presacral regions arising from the neuroforamina. Low-attenuation masses were seen in the psoas musculature as well as scattered throughout the peripheral soft tissues (Figs 2a, 2b, 3a).
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Figure 1a. (a) CT scan obtained with oral and intravenous contrast material shows the large, heterogeneous MPNST (*) in the midpelvis encasing the iliac vessels (small arrowheads). The MPNST was isolated in the abdomen and was not connected to the plexiform neurofibromas that arose from the sacral plexus. The surrounding intestine (small arrows) is displaced peripherally; however, there is no evidence of obstruction. Low-attenuation lesions (large arrows) are seen posterior to the psoas muscles bilaterally as well as within the right psoas muscle and represent neurofibromas. A cutaneous lesion (large arrowhead) is present in the right anterolateral soft tissues. (b) Postmortem specimen shows the MPNST (*), which is large and yellow-tan with some scattered areas of hemorrhage on the surface. An adherent vessel is noted (arrowheads), as well as a dark grayish portion of psoas muscle (arrow) on the far left side.
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Figure 1b. (a) CT scan obtained with oral and intravenous contrast material shows the large, heterogeneous MPNST (*) in the midpelvis encasing the iliac vessels (small arrowheads). The MPNST was isolated in the abdomen and was not connected to the plexiform neurofibromas that arose from the sacral plexus. The surrounding intestine (small arrows) is displaced peripherally; however, there is no evidence of obstruction. Low-attenuation lesions (large arrows) are seen posterior to the psoas muscles bilaterally as well as within the right psoas muscle and represent neurofibromas. A cutaneous lesion (large arrowhead) is present in the right anterolateral soft tissues. (b) Postmortem specimen shows the MPNST (*), which is large and yellow-tan with some scattered areas of hemorrhage on the surface. An adherent vessel is noted (arrowheads), as well as a dark grayish portion of psoas muscle (arrow) on the far left side.
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Figure 2a. (a) CT scan obtained with oral and intravenous contrast material shows low-attenuation neurofibromas (large arrows) that arise from the neuroforamina bilaterally and have the characteristic "dumbbell" appearance, which represents a partly intradural and partly extradural lesion. A low-attenuation mass (*) is noted posterior to the aorta, displacing the vessel anteriorly. This mass represents the uppermost portion of the MPNST. A subcutaneous neurofibroma is noted (small arrow). (b) CT scan obtained caudal to a shows fusiform, nodular, low-attenuation lesions (arrowheads) in the presacral region. The lesions arise from the sacral foramina and surround the rectum and distal sigmoid colon (between arrows); they represent numerous plexiform neurofibromas. (c) Autopsy specimen of the thoracic segment of the spinal cord shows nodular enlargement of the spinal roots, an appearance characteristic of plexiform neurofibromas (arrows) that diffusely infiltrate along an entire nerve trunk, the so-called dumbbell appearance.
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Figure 2b. (a) CT scan obtained with oral and intravenous contrast material shows low-attenuation neurofibromas (large arrows) that arise from the neuroforamina bilaterally and have the characteristic "dumbbell" appearance, which represents a partly intradural and partly extradural lesion. A low-attenuation mass (*) is noted posterior to the aorta, displacing the vessel anteriorly. This mass represents the uppermost portion of the MPNST. A subcutaneous neurofibroma is noted (small arrow). (b) CT scan obtained caudal to a shows fusiform, nodular, low-attenuation lesions (arrowheads) in the presacral region. The lesions arise from the sacral foramina and surround the rectum and distal sigmoid colon (between arrows); they represent numerous plexiform neurofibromas. (c) Autopsy specimen of the thoracic segment of the spinal cord shows nodular enlargement of the spinal roots, an appearance characteristic of plexiform neurofibromas (arrows) that diffusely infiltrate along an entire nerve trunk, the so-called dumbbell appearance.
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Figure 2c. (a) CT scan obtained with oral and intravenous contrast material shows low-attenuation neurofibromas (large arrows) that arise from the neuroforamina bilaterally and have the characteristic "dumbbell" appearance, which represents a partly intradural and partly extradural lesion. A low-attenuation mass (*) is noted posterior to the aorta, displacing the vessel anteriorly. This mass represents the uppermost portion of the MPNST. A subcutaneous neurofibroma is noted (small arrow). (b) CT scan obtained caudal to a shows fusiform, nodular, low-attenuation lesions (arrowheads) in the presacral region. The lesions arise from the sacral foramina and surround the rectum and distal sigmoid colon (between arrows); they represent numerous plexiform neurofibromas. (c) Autopsy specimen of the thoracic segment of the spinal cord shows nodular enlargement of the spinal roots, an appearance characteristic of plexiform neurofibromas (arrows) that diffusely infiltrate along an entire nerve trunk, the so-called dumbbell appearance.
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Figure 3a. (a) CT scan obtained at the midthorax shows a low-attenuation lesion (large arrow) with a small, central region of high attenuation (small arrow) in the left posterior subcutaneous tissues. The appearance of the lesion is analogous to the CT target sign. Note the subpleural lesions (arrowheads) in the left posterolateral region. (b) Photograph of the thoracic cavity exposed at autopsy shows numerous paraspinal (arrows) and subpleural (arrowheads) nodular masses of various sizes, which are compatible with plexiform neurofibromas.
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Figure 3b. (a) CT scan obtained at the midthorax shows a low-attenuation lesion (large arrow) with a small, central region of high attenuation (small arrow) in the left posterior subcutaneous tissues. The appearance of the lesion is analogous to the CT target sign. Note the subpleural lesions (arrowheads) in the left posterolateral region. (b) Photograph of the thoracic cavity exposed at autopsy shows numerous paraspinal (arrows) and subpleural (arrowheads) nodular masses of various sizes, which are compatible with plexiform neurofibromas.
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Pathologic Evaluation
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A postmortem examination was performed. Gross anatomic findings included a 4,500-g, abdominal, retroperitoneal, yellow-tan tumor adherent to the small intestine, psoas muscle, aorta, and vena cava without involving the intima of the great vessels (Fig 1b). Cut surfaces of the tumor disclosed areas of necrosis, cystic degeneration, and hemorrhage. There was 300 mL of brownish ascites. The peritoneum contained several nodular, semifirm, gray-tan masses 4–5 cm in diameter, which represented neurofibromas. Numerous cutaneous and subcutaneous nodules of varying diameter, 0.1–4 cm, were noted on the head, neck, trunk, and extremities and within the thoracic and abdominal cavities. Multiple spinal nerve roots—mostly in the thoracic segment—displayed plexiform neurofibromas, an appearance diagnostic of NF1 (Figs 2c, 3b). A pulmonary saddle embolus was present in the main pulmonary artery with extension primarily into the left pulmonary artery. Microscopic examination of the large abdominal tumor revealed a malignant, high-grade, spindle cell neoplasm with hemorrhage, necrosis, and degenerative changes, findings consistent with MPNST (Fig 4a). The smaller lesions in the abdomen proved to be benign nerve sheath tumors at histologic analysis (Fig 4b).
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Figure 4a. (a) High-power photomicrograph (original magnification, x400; hematoxylin-eosin stain) of the MPNST shows a whorling pattern of spindle cells with irregular nuclei and perivascular accentuation (arrows), an appearance characteristic of MPNST. Malignant tumors demonstrate higher cellularity and more evident nuclear pleomorphism than their benign counterparts. (b) High-power photomicrograph (original magnification, x250; hematoxylin-eosin stain) of a neurofibroma shows fusiform, wavy cells with fine collagenous fibers. Neurofibromas are benign tumors of nerves and typically demonstrate hypocellular smears with loose tissue fragments, a fibrillar ground substance, and clusters of spindle cells.
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Figure 4b. (a) High-power photomicrograph (original magnification, x400; hematoxylin-eosin stain) of the MPNST shows a whorling pattern of spindle cells with irregular nuclei and perivascular accentuation (arrows), an appearance characteristic of MPNST. Malignant tumors demonstrate higher cellularity and more evident nuclear pleomorphism than their benign counterparts. (b) High-power photomicrograph (original magnification, x250; hematoxylin-eosin stain) of a neurofibroma shows fusiform, wavy cells with fine collagenous fibers. Neurofibromas are benign tumors of nerves and typically demonstrate hypocellular smears with loose tissue fragments, a fibrillar ground substance, and clusters of spindle cells.
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Discussion
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Neurofibromas are tumors derived from Schwann cells, fibroblasts, and supporting cells known as perineural cells. Typically, they are benign and manifest as multiple tumors. NF1 is an autosomal dominant genetic disorder with a prevalence of approximately 1 in 4,000 births and no racial predilection. NF1 is characterized by multiple neurofibromas along the peripheral nerves, optic nerve gliomas, sphenoid wing dysplasia, pigmented iris nodules, and hyperpigmented macular skin lesions known as café-au-lait spots (1). It is associated with a gene on chromosome 17. The formation of dermal neurofibromas is a hallmark of NF1 with a characteristic distribution on the trunk and sparing of the extremities (2). With time, neurofibromas may undergo malignant degeneration (3).
At gross examination, neurofibromas appear as firm, gray-white masses. At histologic analysis, neurofibromas contain Schwann cells and nerve fibers that grow in a disorganized fashion and appear as interlacing bundles of elongated cells with intracellular collagen strands (4). There are three types of neurofibromas: localized, diffuse, and plexiform. The vast majority of these lesions are localized and have no association with NF1, although any of these lesions may occur in NF1 (5). Localized neurofibromas are well-delineated, firm lesions with a white and shiny surface and may appear in the dermis or subcutaneous tissues. Plexiform neurofibromas are thick, fusiform, ropelike expansions of nerve roots and peripheral nerve fibers with a mucoid or translucent cut surface. They are generally unencapsulated tumors that blend indistinctly with adjacent connective tissue or peripheral nerves and are diagnostic of NF1. Their gross appearance is often described as a "bag of worms" (5,6). Rapid enlargement of an existing neurofibroma may be a sign of malignant transformation until proved otherwise.
MPNSTs most commonly occur in the deep soft tissues, usually close to a nerve trunk. The most common sites are the sciatic nerve, brachial plexus, and sacral plexus. The past literature referred to MPNST as malignant schwannoma, neurogenic sarcoma, and neurofibrosarcoma. Malignant peripheral nerve sheath tumor is the current term used by the World Health Organization for this highly aggressive tumor. MPNSTs may arise from plexiform neurofibromas, de novo or secondary to radiation therapy (5,7). At histologic analysis, the presence of mitotic figures distinguishes MPNST from otherwise typical neurofibromas. MPNST accounts for approximately 10% of soft-tissue sarcomas, and 40%–60% of MPNSTs arise from cases of NF1 (8). Overall, there is a 4% chance of malignant transformation in NF1 (9).
Clinically, pain is a classic presenting symptom in patients with MPNST. Other findings include masses larger than 2–6 cm with irregular borders and a history of rapid growth. Often, MPNST produces neurologic deficits in the distribution of the involved nerves due to impingement or mass effect (10,11). At CT, the attenuation of neurogenic tumors depends on their histologic characteristics. Neurofibromas typically have low attenuation, which may be related to the fat content of myelin from Schwann cells, the high water content of myxoid tissue, entrapment of fat, and cystic areas of hemorrhage and necrosis (5). Central enhancement or a target appearance may be seen due to the less cellular and vascular myxoid tissue located in the periphery and the more vascular fibrous tissue seen centrally. The characteristic dumbbell lesion, a partly intradural and partly extradural tumor, represents a neurofibroma that expands the intervertebral foramina and may be best appreciated with cross-sectional imaging (5,12). Ultrasound of a neurofibroma reveals a hypoechoic, well-defined mass.
Radiologically, MPNSTs and neurofibromas may appear indistinguishable; however, certain modalities are providing insight for differentiation. Gallium-67 citrate imaging has shown that MPNSTs have greater uptake compared with benign lesions. At magnetic resonance imaging, the different signal intensity characteristics of lesions with a higher degree of anaplasia are proving useful as well. Other factors such as a more rapid and infiltrative growth pattern are particularly helpful in distinguishing the two (5).
Gross inspection of MPNSTs reveals a fusiform, fleshy, tan-white mass with areas of degeneration and secondary hemorrhage. The nerve proximal and distal to the tumor may be thickened due to spread of the tumor along the epineurium and perineurium. At histologic analysis, MPNSTs are unencapsulated infiltrating tumors composed of spindle cells arranged in a whorling pattern with irregular nuclei, cyst formation, and nuclear palisading (13). Mitotic figures are readily visible, with more than one per high-power field, and 50%–90% of cases are immunoreactive with S100 protein staining (14).
Surgical resection is the first line of therapy, ideally with total removal of the tumor. Owing to a high risk of recurrence with incomplete resection, postoperative irradiation and chemotherapy are necessary; however, they are often used as adjuvant therapy even if the tumor is completely resected. Even with aggressive therapy, local recurrence of tumor is seen in 50% of patients (5). Hematogenous metastatic spread occurs most commonly to the lungs. The reported 5-year survival rate for patients with MPNST without NF1 is as high as 50%. It drops to as low as 10% for MPNST patients with NF1 (15).
Genetic counseling of family members suspected to have this disease should be performed. The patient presented in this report had an incomplete surgical resection due to the size and location of his lesion and died of pulmonary emboli while awaiting radiation therapy.
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Footnotes
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2**. Multiple body systems 
Abbreviations: MPNST = malignant peripheral nerve sheath tumor,
NF1 = neurofibromatosis type 1
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References
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- Mulvihill JJ. Malignancy: epidemiologically associated cancers. In: Huson SM, Hughes RAC, eds. The neurofibromatoses: a pathogenetic and clinical overview. Cambridge, England: Cambridge University Press, 1994; 305-315.
- Riccardi VM. Neurofibromatosis: phenotype, natural history, and pathogenesis Baltimore, Md: Johns Hopkins University Press, 1992; 18-28.
- Ducatman BS, Scheihauer BW, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 120 cases. Cancer 1986; 57:2006-2021.[CrossRef][Medline]
- Wanebo JE, Malik JM, Vandenberg SR, Wanebo HJ, Driesen N, Persing JA. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 28 cases. Cancer 1993; 71:1247-1253.[CrossRef][Medline]
- Murphey MD, Smith WS, Smith SE, Kransdorf MJ, Temple HT. Imaging of musculoskeletal neurogenic tumors: radiologic-pathologic correlation. RadioGraphics 1999; 19:1253-1280.[Abstract/Free Full Text]
- Oda Y, Hashimoto H, Tsuneyoshi M, Iwata Y. Benign glandular peripheral nerve sheath tumor: a case report. Pathol Res Pract 1994; 190:466-473.[Medline]
- Robbins P, Papadimitriou J. Glandular peripheral nerve sheath tumors. Pathol Res Pract 1994; 190:412-415.[Medline]
- Wick MR, Swanson PE, Scheithauser BW, Manivel JC. Malignant peripheral nerve sheath tumor: an immunohistochemical study of 62 cases. Am J Clin Pathol 1987; 87:425-433.[Medline]
- Meis JM, Enzinger FM, Martz KL, et al. Malignant peripheral nerve sheath tumor (malignant schwannoma) in children. Am J Surg Pathol 1992; 16:694-707.[Medline]
- Daimaru Y, Hashimoto H, Enjoji M. Malignant peripheral nerve sheath tumor (malignant schwannoma): an immunohistochemical study of 29 cases. Am J Surg Pathol 1985; 9:434-444.[Medline]
- Enzinger FM, Weiss SW. Soft tissue tumors 3rd ed. St Louis, Mo: Mosby–Year Book, 1995; 829-837, 889–910.
- Haaga JR, Lanzieri CF, Sartorius DJ, Zerhouni EA. Cervical adenopathy and neck masses. In: Holliday RA, Reede DL, eds. Computed tomography and magnetic resonance imaging of the whole body. 3rd ed, vol 1. St Louis, Mo: Mosby–Year Book, 1994; 541-543.
- Cotran RS, Kumar V, Robbins SL. Robbins pathologic basis of disease 5th ed. Philadelphia, Pa: Saunders, 1994.
- Johnson MD, Glick AD, Davis BW. Immunohistochemical evaluation of Leu-7, myelin basic protein, S-100 protein, glial fibrillary acidic protein, and LN3 immunoreactivity in nerve sheath tumors and sarcomas. Arch Pathol Lab Med 1988; 112:155-160.[Medline]
- Doorn PF, Molenaar WM, Butler J, Hoekstra HJ. Malignant peripheral nerve sheath tumors in patients with and without neurofibromatosis. Eur J Surg Oncol 1995; 21:78-82.[CrossRef][Medline]
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History
Imaging Findings
