MRI Features in the Differentiation of Malignant Peripheral Nerve Sheath Tumors and Neurofibromas
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1 Musculoskeletal Imaging Original Research Wasa et al. MRI of Peripheral Nerve Sheath Tumors and Neurofibromas Musculoskeletal Imaging Original Research Junji Wasa 1 Yoshihiro Nishida 1 Satoshi Tsukushi 1 Yoji Shido 1 Hideshi Sugiura 2 Hiroatsu Nakashima 3 Naoki Ishiguro 1 Wasa J, Nishida Y, Tsukushi S, et al. Keywords:, MRI, neurofibroma, neurofibromatosis 1 DOI: /JR Received March 11, 2009; accepted after revision November 18, This work was supported in part by The Nakatomi Foundation and by the Ministry of Education, ulture, Sports, Science and Technology of Japan (Grant-in-id for Scientific Research). 1 Department of Orthopaedic Surgery, Nagoya University Graduate School and School of Medicine, 65-Tsuruma, Showa, Nagoya , Japan. ddress correspondence to Y. Nishida (ynishida@med.nagoya-u.ac.jp). 2 Department of Orthopaedic Surgery, ichi ancer enter Hospital, Nagoya, Japan. 3 Department of Orthopaedic Surgery, ichi ancer enter, ichi Hospital, Okazaki, Japan. JR 2010; 194: X/10/ merican Roentgen Ray Society MRI Features in the Differentiation of Malignant Peripheral Nerve Sheath Tumors and Neurofibromas OJETIVE. The objective of this study was to identify the MRI criteria that best differentiate from benign neurofibromas. MTERILS ND METHODS. We retrospectively analyzed MR images obtained for 41 histologically diagnosed cases of malignant peripheral nerve sheath tumor and 20 cases of neurofibroma that had been treated at four tertiary institutions. Twenty of the patients with and 14 patients with neurofibromas developed the disease in association with neurofibromatosis 1. The MR images were evaluated with regard to tumor size, signal intensity, heterogeneity of T1- and T2-weighted MR images, enhancement pattern, definition of margins, presence of perilesional edemalike zone, and presence of intratumoral cystic lesions. RESULTS. Significant differences between and neurofibromas were noted for the largest dimension of the mass, peripheral enhancement pattern, perilesional edemalike zone, and intratumoral cystic lesion. In cases associated with neurofibromatosis 1, heterogenicity on T1-weighted images was also significant in differentiating neurofibroma from malignant peripheral nerve sheath tumor. The presence of two or more of the four features suggestive of malignancy indicated malignant peripheral nerve sheath tumor with a sensitivity of 61% and a specificity of 90%. ONLUSION. The MR features described in this study are useful for distinguishing from neurofibromas. If a tumor has two or more of the four statistically significant features, it can be considered to be highly suspicious of malignancy and should be subjected to a biopsy for early diagnosis. M alignant peripheral nerve sheath tumors are rare tumors that account for approximately 3 10% of all soft-tissue sarcomas [1, 2]. have a tendency to recur locally and to metastasize and are known to be highly malignant. In 25 50% of cases, malignant peripheral nerve sheath tumors are associated with neurofibromatosis 1. neurofibromatosis 1 is the most important risk factor for developing malignant peripheral nerve sheath tumor, and patients with deep-seated plexiform neurofibromas are at particular risk of malignant transformation [3]. malignant peripheral nerve sheath tumors in patients with neurofibromatosis 1 are likely to be larger [4] because of the longer time until diagnosis. It is necessary to diagnose malignant peripheral nerve sheath tumors at an early stage. However, it is difficult to differentiate malignant peripheral nerve sheath tumors from neurofi- bromas, particularly in patients with neurofibromatosis 1. If a tumor is located in a superficial trunk or extremity area, a biopsy can be performed relatively easily. However, in cases in which a biopsy may cause nerve palsy or dissemination of malignant tumor cells in visceral organs, it is occasionally difficult to perform a biopsy for a tumor located in the visceral or retroperitoneum area, which is where neurofibromas frequently develop in patients with neurofibromatosis 1. Previous reports described the differentiation of benign and malignant peripheral nerve sheath tumors by use of imaging features [5 8]. These studies described several imaging features that were useful in differentiating malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors. However, few studies have shown in a convincing manner the differentiation of from neurofibromas in larger series JR:194, June 2010
2 MRI of Peripheral Nerve Sheath Tumors and Neurofibromas The aim of this study was to identify useful MRI findings in differentiating between and neurofibromas, including the sporadic type and the neurofibromatosis 1 associated type. Materials and Methods Patient haracteristics This retrospective review of medical records and MR images was approved by the institutional review boards of our institutions. etween 1990 and 2007, 41 patients with malignant peripheral nerve sheath tumor and 20 patients with neurofibroma who had been treated at four tertiary institutions were enrolled in this study. ll diagnoses were confirmed by experienced pathologists. Twenty of the patients with malignant peripheral nerve sheath tumors and 14 of the patients with neurofibroma developed the disease in association with neurofibromatosis 1. Thirteen cases of low-grade malignant peripheral nerve sheath tumor were included. Low-grade malignant peripheral nerve sheath tumor is diagnosed when there is generalized nuclear atypia, increased cellularity, and, typically, low levels of mitotic activity. ccording to the Fédération Nationale des entres de Lutte ontre le ancer grade system, grades 1 and 2 were defined as low grade in this study. There were 32 males and 29 females, ranging in age from 16 to 83 years (average, 41.6 years). The location of malignant peripheral nerve sheath tumors was an extremity in 19 cases (upper extremity in seven cases and lower extremity in 12 TLE 1: Demographic haracteristics of Patients with malignant peripheral nerve sheath tumor (PNST) or Neurofibroma Sex haracteristic Malignant PNST (n = 41) Neurofibroma (n = 20) Male Female 20 9 ge (y), median (range) 41 (16 83) 35 (19 71) Neurofibromatosis Tumor depth Deep Superficial 4 4 cases) and a trunk in 22 cases (paraspinal in seven cases, retroperitoneal in six cases, and brachial plexus in four cases); the location of neurofibromas was an extremity in 13 cases (upper extremity in three cases and lower extremity in 10 cases) and a trunk in seven cases. Table 1 lists additional patient characteristics. MRI MRI was performed in our own or affiliated institutions using a variety of systems with a field strength of T. The images were obtained in a combination of coronal, sagittal, and axial planes. Surface coils appropriate to the site being imaged were used. In all cases, the diagnosis was confirmed with a pathologic specimen. The MRI sequences varied because of the wide referral base to each institution. ll patients in the study group underwent both T1- and T2-weighted sequences, and gadolinium-enhanced images were available for 25 patients with malignant peripheral nerve sheath tumors and for 12 patients with neurofibromas. The MR images were reviewed by two investigators and were evaluated with regard to tumor size (maximum tumor dimension), signal intensity (compared with the intensity of muscle), heterogeneity (different signal intensities of the internal structure) of T1- and T2-weighted pulse sequences, enhancement pattern (peripheral or not), definition of margins, presence of perilesional edemalike zone, and presence of intratumoral cystic lesions. The enhancement pattern was classified according to the presence or absence of peripheral enhancement using gadolinium-enhanced images (Fig. 1). Fig year-old man with neurofibromatosis 1, with malignant peripheral nerve sheath tumor in left thigh., oronal T1-weighted MR image shows heterogeneous pattern., oronal T2-weighted MR image also shows heterogeneous pattern., oronal T1-weighted fat-saturated gadolinium-enhanced MR image shows peripheral enhancement pattern. JR:194, June
3 Wasa et al. Tumor margin was classified as either well or ill defined, according to the presence or absence of a low-intensity rim on T1- and T2-weighted images and any invasion to adjacent bony or soft-tissue structures. Perilesional edemalike zone was assessed according to whether a feathery zone of high signal intensity was seen in the surrounding tissues, outside the capsule, on T2-weighted images (Fig. 2). The presence of intratumoral cystic lesions was determined according to the finding of hypointensity to muscle on T1-weighted and marked hyperintensity on T2-weighted images (Fig. 3). Fig year-old man with malignant peripheral nerve sheath tumor who presented with pain and enlarging mass in left upper arm., oronal T2-weighted MR image shows presence of perilesional edemalike zone (arrowheads) outside area of low signal intensity (arrows)., oronal T1-weighted MR image shows isointense signal of tumor relative to muscle., Image shows microscopic pathologic findings of perilesional edemalike zone. Tumor (T) has pseudocapsule (P). Myxomatous stroma (MS) and empty spaces (E) separating muscular fibers (M) are consistent with edematous reaction outside pseudocapsule without tumor cell invasion. Statistical nalysis The recorded data were analyzed using statistical database software (SPSS 11.0 software for Microsoft Windows). Differences in imaging characteristics between malignant peripheral nerve sheath tumor and neurofibroma were compared using chi-square test or Fisher s exact test, for categorized variables, and Mann-Whitney U test, for continuous variables. p value of < 0.05 was considered statistically significant. Results Table 2 shows the MRI features analyzed. The median lesion size was 9.9 cm (1 20 cm) in patients with malignant peripheral nerve sheath tumor and 5 cm (2 20 cm) in patients with neurofibroma (p = 0.029). On the T1- weighted images, 14 (70%) of 20 neurofibromas were homogeneous and isointense relative to skeletal muscle, and six (30%) of 20 neurofibromas showed slightly high intensity in some areas of the tumor (Fig. 4), whereas 21 (51%) of 41 malignant peripheral nerve sheath tumors were heterogeneous. On the T2-weighted images, 14 (70%) of 20 neurofibromas and 32 (78%) of 41 malignant peripheral nerve sheath tumors were heterogeneous. There was no significant difference in heterogeneity on the T1- and T2-weighted images for all patients and for patients without neurofibromatosis 1. On the gadolinium-enhanced T1-weighted images, tumors with the peripheral enhancement pattern were noted in 14 of 25 malignant peripheral nerve sheath tumors and in one of 12 neurofibromas (p = 0.006). Perilesional edemalike zones were present in 12 of 41 malignant peripheral nerve sheath tumors, but not in any of the neurofibromas (p = 0.005). n intratumoral cystic lesion was identified in 16 of Fig year-old woman with malignant peripheral nerve sheath tumor in right retroperitoneum area., xial T1-weighted MR image shows mass with isointense signal., xial T2-weighted MR image shows cystic lesion and presence of hemorrhage with fluid level (arrows)., xial T1-weighted fat-saturated gadolinium-enhanced MR image shows peripheral enhancement pattern JR:194, June 2010
4 MRI of Peripheral Nerve Sheath Tumors and Neurofibromas TLE 2: MRI features analyzed in ll cases Feature Malignant PNST (n = 41) Neurofibroma (n = 20) p Largest tumor size (cm), median (range) 10 (1 20) 5 (1.5 20) Heterogeneity on T1-weighted image Homogeneous Heterogeneous 21 6 Heterogeneity on T2-weighted image Homogeneous 9 6 Heterogeneous Enhancement pattern Peripheral enhancement present 14 1 Peripheral enhancement absent No enhanced image obtained 16 8 Perilesional edema Present 12 0 bsent Intratumoral cystic change 0.02 Present 16 2 bsent Margin definition Well defined Ill defined 10 3 Note hi-square test or Fisher s exact test was used to analyze the heterogeneity on T1-weighted and T2-weighted images, enhancement pattern, presence of perilesional edema, presence of intratumoral cystic lesion, and margin definition. Mann-Whitney U test was used to analyze the largest tumor size. PNST = peripheral nerve sheath tumor. 41 and in two of 20 neurofibromas (p = 0.02). Thirty-one of 41 patients with malignant peripheral nerve sheath tumors and 17 of 20 patients with neurofibromas had tumors with well-defined margins; there was no statistically significant difference in tumor margin. Target sign, which was reported to be a pathognomonic finding for neurofibroma but lacked sensitivity, was also evaluated. s expected, only two of 14 neurofibromas (low sensitivity for neurofibroma) and none of 20 (high specificity for neurofibroma) showed the target sign. Next, we evaluated MR images for 34 patients with neurofibromatosis 1 (Table 3). Significant differences were noted in tumor size (p = 0.002), heterogeneity on T1-weighted images (p = 0.001), presence of peripheral enhanced pattern on gadolinium-enhanced T1-weighted images (p = 0.002), presence of perilesional edemalike zone (p < 0.001), and presence of intratumoral cystic change (p = 0.01) between the 20 patients with malignant peripheral nerve sheath tumor and the 14 patients with neurofibroma associated with neurofibromatosis 1. Finally, the differentiating score was calculated by adding the scores for each MR image feature that was significantly different between malignant peripheral nerve sheath tumor and neurofibroma (Table 4). s a result, 25 (61%) of 41 malignant peripheral nerve sheath tumors had more than two features, in contrast to only two (10%) of 20 neurofibromas. Thirteen (32%) of 41 malignant peripheral nerve sheath tumors and none (0%) of 20 neurofibromas had more than three features. Only four (9.8%) of 41 had all four features. For all malignant peripheral nerve sheath tumor cases, the presence of more than two MR image features showed 61% sensitivity and 90% specificity; for high-grade malignant peripheral nerve sheath tumor cases only, the presence of more than two of these features showed 64% sensitivity and 90% specificity. Discussion We identified four statistically significant MRI features that helped to distinguish malignant peripheral nerve sheath tumors from neurofibromas: increased largest dimension of the mass, presence of peripheral enhanced pattern, presence of perilesional edemalike zone, and presence of intratumoral cystic lesion. For cases associated with neurofibromatosis 1, Fig year-old man with neurofibromatosis 1, with neurofibroma in left thigh., xial T1-weighted MR image shows slightly heterogeneous pattern., xial T2-weighted MR image shows also heterogeneous pattern., xial T1-weighted gadolinium-enhanced MR image shows heterogeneous enhancement pattern. JR:194, June
5 Wasa et al. TLE 3: MRI features analyzed in the cases with neurofibromatosis 1 Feature Malignant PNST (n = 20) Neurofibroma (n = 14) p Largest tumor size (cm), median (range) 14.5 (4 20) 6 (2.5 20) Heterogeneity on T1-weighted image Homogeneous 3 10 Heterogeneous 17 4 Heterogeneity on T2-weighted image Homogeneous 1 4 Heterogeneous Enhancement pattern Peripheral enhancement present 9 1 Peripheral enhancement absent 2 9 No enhanced image obtained 9 4 Perilesional edema < Present 8 0 bsent Intratumoral cystic change 0.01 Present 10 1 bsent Margin definition Well defined Ill defined 5 3 Note PNST = peripheral nerve sheath tumor. TLE 4: Total points of significant MR image features that differentiate between (PNSTs) and neurofibromas Type of Tumor heterogeneity on the T1-weighted images was also a useful MRI feature. These factors had been noted in previous reports, but the present series comprising 41 patients with malignant peripheral nerve sheath tumor represents a particularly large number of patients with this rare soft-tissue sarcoma. Other studies have previously described MRI features of malignant peripheral nerve sheath tumor and neurofibroma. Li et al. [6] reported that imaging features suggestive of malignancy may include larger size, lack of contiguity with adjacent specific nerves, and an infiltrative margin. Those results are partly in agreement with ours in that an increased largest dimension of the mass and presence of perilesional edemalike zone were found by us to be significant features differentiating malignancy Total Points Malignant PNST (n = 28) Low-grade malignant PNST (n = 13) Neurofibroma (n = 20) from benignancy. However, the study by Li et al. [6] included only nine patients with malignant peripheral nerve sheath tumor and lacked the description of neurofibromatosis 1. hargava et al. [5] reported that a target sign, a central hypointense region seen on T2-weighted images, may be helpful in distinguishing benign from malignant tumors. The appearance of such a target sign may be caused by intralesional necrosis and hemorrhage. In our study, two of 14 neurofibromas and none of 20 malignant peripheral nerve sheath tumors showed this sign. ecause most neurofibromas did not show this sign in this study, it might not be helpful to differentiate between benign and malignant lesions. Ogose et al. [7] showed that, after administration of gadopentetate dimeglumine, malignant peripheral nerve sheath tumor shows peripheral enhancement on T1-weighted images, as opposed to focal central enhancement, which is often observed in benign neurogenic tumors. Their study analyzed only eight patients with neurofibroma and 16 with malignant peripheral nerve sheath tumor and showed that schwannoma occasionally had peripheral enhancement. In our study, only one case of neurofibroma showed a peripheral enhancement pattern, suggesting that this pattern may be a more relevant criterion for differentiating malignant peripheral nerve sheath tumor from neurofibroma. Intratumoral cystic change commonly occurs as a result of hemorrhage or necrosis in schwannoma, but rarely in neurofibroma [8]. This feature can assist in the differentiation of neurofibroma from malignant peripheral nerve sheath tumor, in which malignant transition may result in the occurrence of necrosis or hemorrhage. lthough cystic change often is coincident with peripheral enhancement, there were five of 14 cases with peripheral enhancement without cyst formation in malignant peripheral nerve sheath tumors (Fig. 5). Heterogeneity on T1-weighted images was observed in 17 (85%) of 20 cases in malignant peripheral nerve sheath tumors with neurofibromatosis 1 in this study. This feature is not a significant factor in all cases but is significant in neurofibromatosis 1 cases. Malignant transformation of the tumor from a preexisting benign neurofibroma might cause necrosis or hemorrhage of the tumor or both, which will be reflected as heterogeneity on T1-weighted images. More patients should be analyzed further to clarify this issue. Matsumine et al. [9] analyzed 19 cases of malignant peripheral nerve sheath tumor associated with neurofibromatosis 1 and reported that the heterogeneous area on T1-weighted images is a diagnostic indicator with multivariate analysis. Together with the results of their study, heterogeneity on T1-weighted images will be a useful feature for defining malignant peripheral nerve sheath tumors associated with neurofibromatosis 1. However, they did not describe the low-grade malignant peripheral nerve sheath tumor, which is more difficult to differentiate from neurofibromas. ggressiveness of malignant peripheral nerve sheath tumor may cause a perilesional edemalike reaction. In the present study, eight of 20 showed perilesional edemalike zones, but none of 14 neurofibromas did. Malignant peripheral nerve sheath tumors with a perilesional 1572 JR:194, June 2010
6 MRI of Peripheral Nerve Sheath Tumors and Neurofibromas edemalike zone had well-defined margins. perilesional edemalike zone was observed as a feathery zone outside the tumor pseudocapsule with hyperintense signal on T2-weighted images (Fig. 2). Ill-defined margins may reflect marginal invasion of the tumor into the tissue contiguous to the tumor. Well-defined tumor margins were seen in most cases of malignant peripheral nerve sheath tumor (76%) and neurofibroma (85%), with no statistically significant difference noted between them. Van Herendael et al. [10] reported that MR images of showed significantly well-defined or partially ill-defined margins compared with those of nonneurogenic malignant soft-tissue tumors. Fig year-old man with neurofibromatosis 1, with plexiform neurofibroma showing rapid enlargement, resulting from malignant transformation in right thigh., oronal T1-weighted MR image shows mass (arrows) with slightly heterogeneous signal intensity., oronal T2-weighted fat-saturated MR image shows large mass (arrows) of heterogeneously high intensity but no cystic change and plexiform neurofibroma (arrowheads) in right thigh., oronal T1-weighted fat-saturated gadolinium-enhanced MR image shows peripheral enhancement pattern (arrows). Margin features thus are not be helpful in distinguishing malignancy from benignancy. In the evaluation of neurogenic tumors, the presence of irregular perilesional high signal (representing either edemalike zone or tumor invasion) suggests malignant peripheral nerve sheath tumor, although in only 40% of cases. With regard to the four significant MRI features, the presence of two to four of those features is suggestive of malignancy (specificity, 90%; sensitivity, 61%) (Table 4). linical features may support the differentiation between and neurofibromas. Pain at rest and severe motor weakness strongly suggest malignancy [7], and short duration of symptoms and the presence of pain are also significantly associated with malignancy [11]. On the other hand, another study indicated that the presence of pain cannot be used as an indicator of malignancy [12]. The 1997 consensus guidelines for treatment of patients with neurofibromatosis 1 state that imaging studies should not be undertaken unless the clinical examination identifies problems that require such studies [13]. onsidering that individuals with deep plexiform neurofibromas are 20 times more likely to have malignant peripheral nerve sheath tumor than those without deep plexiform neurofibromas [14], patients with not only clinical manifestations but also with risk factors such as deep plexiform neurofibroma require MRI evaluation. Fig year-old man with neurofibromatosis 1, with neurofibroma in left side of neck., xial T1-weighted MR image shows multilobular masses of isointense signal relative to surrounding muscle., xial T2-weighted MR image shows masses of high signal intensity relative to surrounding muscle., Tumor is patchy-enhanced on axial T1-weighted fat-saturated gadolinium-enhanced MR image. Tumor has only one of four statistically significant features (size, > 5 cm). Tumor did not show rapid growth; patient had no neck pain. Patient was carefully followed up. JR:194, June
7 Wasa et al. Moreover, patients with the significant features suggestive of malignant peripheral nerve sheath tumor described in this study need immediate biopsy to determine the pathologic diagnosis. This study has several limitations. First, this study focused on neurofibroma and malignant peripheral nerve sheath tumor and did not include evaluation for differentiation from schwannoma. In patients without neurofibromatosis 1, differentiation of malignant peripheral nerve sheath tumor from schwannoma is also important because schwannoma often shows cystic formation. Second, there was a relatively high rate (32%) of lowgrade in this study compared with that in previous studies (18 22%) [3, 4]. However, the sensitivity and specificity were not different whether in all malignant peripheral nerve sheath tumor cases (61% and 90%, respectively) or in only high-grade malignant peripheral nerve sheath tumor cases (64% and 90%, respectively). In our institution, routine MRI examination for neurofibromas in patients with neurofibromatosis 1 would lead us to early detection of malignant transformation of the tumors and would affect the high percentage of low-grade malignant peripheral nerve sheath tumor cases. Third, we collected the MRI data from four institutions; the MRI sequences were not standardized among the institutions, and gadolinium enhancement was used in only a limited number of cases. However, previous studies analyzing MRI features in patients with neurogenic tumors had even fewer patients than this study because of the rarity of this tumor. We conclude that, on the basis of the analysis of 41 cases of malignant peripheral nerve sheath tumor and 20 cases of neurofibroma, the four significant features of MRI described in this study increased largest dimension of the mass, presence of peripheral enhanced pattern, presence of perilesional edemalike zone, and presence of intratumoral cystic lesion are useful for distinguishing between and neurofibromas. The presence of two to four of these features is suggestive of malignancy (specificity, 90%; sensitivity, 61%). This study, thus, is of value in identifying the MRI features useful for deciding whether to perform a biopsy, in combination with consideration of the clinical symptoms. If a tumor has two or more of the four statistically significant features, it can be considered to be highly suspicious of malignancy and should be subjected to a biopsy for early diagnosis. If a tumor has only one feature (Fig. 6), it should be determined whether to perform a biopsy or to initiate follow-up to examine clinical features, such as pain at rest and severe motor deficit. cknowledgments We thank Eri Ishihara for secretarial assistance and Yoshie Shimoyama for critical histologic evaluation of resected specimens. References 1. Grobmyer SR, Reith JD, Shahlaee, ush H, Hochwald SN. Malignant peripheral nerve sheath tumor: molecular pathogenesis and current management considerations. J Surg Oncol 2008; 97: Enzinger FM, Weiss SW. Malignant tumours of peripheral nerves. In: Enzinger FM, Weiss SW, eds. Soft tissue tumors, vol. 31. St. Louis, MO: Mosby ompany, 2001: Ducatman S, Scheithauer W, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 120 cases. ancer 1986; 57: nghileri M, Miceli R, Fiore M, et al. Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. ancer 2006; 107: hargava R, Parham DM, Lasater OE, hari RS, hen G, Fletcher D. MR imaging differentiation of benign and malignant peripheral nerve sheath tumors: use of the target sign. Pediatr Radiol 1997; 27: Li S, Huang GS, Wu HD, et al. Differentiation of soft tissue benign and malignant peripheral nerve sheath tumors with magnetic resonance imaging. lin Imaging 2008; 32: Ogose, Hotta T, Morita T, et al. Tumors of peripheral nerves: correlation of symptoms, clinical signs, imaging features, and histologic diagnosis. Skeletal Radiol 1999; 28: Levine E, Huntrakoon M, Wetzel LH. Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques. JR 1987; 149: Matsumine, Kusuzaki K, Nakamura T, et al. Differentiation between neurofibromas and malignant peripheral nerve sheath tumors in neurofibromatosis 1 evaluated by MRI. J ancer Res lin Oncol 2009; 135: Van Herendael H, Heyman SR, Vanhoenacker FM, et al. The value of magnetic resonance imaging in the differentiation between malignant peripheral nerve-sheath tumors and non-neurogenic malignant soft-tissue tumors. Skeletal Radiol 2006; 35: Furniss D, Swan M, Morritt DG, et al. 10-year review of benign and malignant peripheral nerve sheath tumors in a single center: clinical and radiographic features can help to differentiate benign from malignant lesions. Plast Reconstr Surg 2008; 121: oleman G, rger PH, Dalinka MK, Obringer, Raney R, Meadows T. T of sarcomatous degeneration in neurofibromatosis. JR 1983; 140: Gutmann DH, ylsworth, arey J, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JM 1997; 278: Tucker T, Wolkenstein P, Revuz J, Zeller J, Friedman JM. ssociation between benign and malignant peripheral nerve sheath tumors in NF1. Neurology 2005; 65: JR:194, June 2010
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