Soft Tissue Diffuse Neurofibromas
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1 ase Series Soft Tissue Diffuse Neurofibromas Sonographic Findings Wen hen, MD, Jian-Wen Jia, MD, Jin-Rui Wang, MD Objective. The purpose of this study was to describe the sonographic findings of soft tissue diffuse neurofibromas. Methods. Seven soft tissue diffuse neurofibromas proven pathologically were retrospectively evaluated. Medical records and histologic examinations were reviewed, and sonograms were analyzed for the echogenicity, location, margin, and vascularity. Results. ll identified lesions were hyperechoic masses permeated by multiple interconnecting irregular hypoechoic tubular or nodular structures. ll lesions were located in the subcutaneous fat zone, and all had poorly defined margins with adjacent normal subcutaneous fat. The margins between the lesions and the adjacent muscles were well defined in 5 and poorly defined in the other 2. The vascularity was extensive in 5 lesions and scarce in the other 2. onclusions. Soft tissue diffuse neurofibromas have a characteristic sonographic appearance; therefore, sonography should be considered a useful tool in the initial screening of this disease. Key words: diffuse neurofibroma; soft tissue; sonography. bbreviations MRI, magnetic resonance imaging; NF1, neurofibromatosis type 1 Received October 4, 2006, from the Department of Diagnostic Ultrasound, Peking University Third Hospital, eijing, hina. Revision requested October 24, Revised manuscript accepted for publication November 2, We thank rthur. Fleischer, MD, and manda. Squires, MD (Department of Radiology and Radiological Sciences, Vanderbilt University Medical enter, Nashville, TN), for assistance. ddress correspondence to Wen hen, MD, Department of Diagnostic Ultrasound, Peking University Third Hospital, eijing, hina. chenwen7989@yahoo.com Soft tissue neurofibromas represent slightly more than 5% of benign soft tissue neoplasms and most frequently affect patients who are 20 to 30 years old. 1 Pathologically, neurofibromas can be divided into 3 types: localized, plexiform, and diffuse. The localized neurofibroma appears as an ovoid or a fusiform mass involving the nerve, which may be seen entering and exiting the tumor mass. The plexiform neurofibroma diffusely involves a long segment of the nerve and its branches and has a serpentinelike appearance. The diffuse neurofibroma is characterized by infiltrative growth in the subcutaneous fat and subsequent entrapment of the normal surrounding structures. soft tissue diffuse neurofibroma is an uncommon pattern, which occurs principally in children and young adults. It is most common in the head and neck region and appears clinically as a plaquelike elevation of the skin. 2 To date, sonographic evaluation of soft tissue diffuse neurofibromas has been limited. To our knowledge, it has been described only in 2 cases. In these cases, it appeared as either a poorly defined hypoechoic mass with high flow in relatively large blood vessels or subcutaneous infiltrative hypoechoic nodules with increased vascularity. 3,4 Here we report 7 patients with soft tissue diffuse neurofibromas proven pathologically. The purpose of this study was to describe the sonographic findings of soft tissue diffuse neurofibromas by the merican Institute of Ultrasound in Medicine J Ultrasound Med 2007; 26: /07/$3.50
2 Soft Tissue Diffuse Neurofibromas Materials and Methods Electronic pathologic records from December 2002 to December 2005 at our hospital were searched for the term soft tissue diffuse neurofibroma, and matching records were identified and reviewed retrospectively. Only patients who underwent sonographic imaging at our institution were included in the study. The electronic record search yielded 13 patients with soft tissue diffuse neurofibromas from 2002 to 2005, and the diagnosis of soft tissue diffuse neurofibroma was confirmed in all patients histologically after surgical resection. Of these, 7 patients underwent sonography at our institution. Our study received approval from our hospital s Institutional Review oard. The need for informed consent was waived for this retrospective study. These 7 patients included 4 male and 3 female (age range, years; mean, 21 years); 5 of them also had a clinical diagnosis of neurofibromatosis type 1 (NF1) according to established clinical criteria for NF1 (the presence of 2 or more of the following: café au lait macules, neurofibromas, Lisch nodules, axillary or inguinal freckling, optic glioma, distinctive osseous lesions, and a first-degree relative with NF1 5,6 ). Three radiologists with sonographic experience of 8, 15, and 20 years performed the sonographic examinations with an HDI 3000 system (Philips Medical Systems, othell, W), an cuson-sequoia system (Siemens Medical Solutions, Mountain View, ), or a LOGIQ 9 system (GE Healthcare, Milwaukee, WI) using a variety of linear array transducers with frequencies ranging from 5 to 15 MHz. Seven sonograms, clinical records, and histologic examinations were reviewed retrospectively. The sonograms were analyzed for the echogenicity, location, margin, and vascularity by a radiologist (W..) with sonographic experience of 15 years. The echogenicity was determined as hypoechoic or hyperechoic by comparing the lesion with the adjacent normal soft tissues. The margins were determined to be poorly defined with a wide zone of the transition ( 5 mm) or well defined with a narrow zone of transition (<5 mm). olor Doppler flow images were analyzed, and the vascularity of the mass was classified as either hypovascular or hypervascular by comparing with the adjacent muscles. Results The clinical data are summarized in Table 1. ll 7 patients showed a large, soft, compressible, nonpainful subcutaneous mass with the largest dimension ranging from 5 to 34 cm. Six patients had brown hyperpigmented skin overlapping the lesions; the other lesion was covered by normal skin. On gray scale sonography, all the lesions were hyperechoic masses permeated by multiple interconnecting irregular hypoechoic tubular or nodular structures (Figures 1 4). These hypoechoic tubular or nodular structures were unevenly distributed and were of a relatively moderate amount in 5 lesions (Figures 1 and 2), of a little amount in 1 lesion (Figure 3), and of a great amount in the other lesion (Figure 4). In 2 lesions, several anechoic ductal structures were also observed (Figure 4). ll lesions were located in the subcutaneous fat zone. Five lesions were seen as clearly confined within the subcutaneous fat zone and had well-defined borders with the adjacent muscles (Figure 2); the other 2 were seen as partially infiltrating into the adjacent muscles and therefore had poorly defined margins with these muscles (Figure 4). The margins between the lesions and the adjacent subcutaneous fat were poorly defined in all the lesions (Figure 3). On color Doppler sonography, 5 lesions were hypervascular masses (Figure 2); the other 2 were hypovascular masses (Figures 1 and 3). The 2 lesions with anechoic ductal structures belonged to the group of hypervascular masses, and those ductal structures were found to be dilated blood vessels (Figure 4). Table 1. linical Data of Patients With Soft Tissue Diffuse Neurofibroma ase ge, y Sex Location NF Male Head Yes 2 25 Female Head No 3 14 Male hest Yes 4 28 Male Hip Yes 5 22 Female ack Yes 6 19 Male Hip No 7 18 Female ack Yes 514 J Ultrasound Med 2007; 26:
3 hen et al Figure 1. Soft tissue diffuse neurofibroma in a 22-year-old female patient., Gray scale sonogram showing hypoechoic tubular (arrows) and nodular (arrowheads) structures within the hyperechoic subcutaneous lesion., olor Doppler sonogram showing only a few vessels within the lesion (arrow)., Photomicrograph of a surgical specimen showing extensive fat (arrows) and small intratumoral vessels (arrowheads). Histologic examination of the excised specimens in all cases showed diffuse neurofibromas, which were characterized by diffuse proliferation of neurofibromatous tissues within the subcutaneous fat. The amounts of neurofibromatous tissues in each case correlated well with the amounts of hypoechoic structures found on sonography (Figures 1 4). Multiple intratumoral blood vessels were seen in all lesions. Figure 2. Soft tissue diffuse neurofibroma in a 14-year-old male patient., Gray scale sonogram showing hypoechoic tubular structures (arrowheads) within the hyperechoic subcutaneous lesion. Note that the margin between the mass and the adjacent muscle is well defined (arrows)., olor Doppler sonogram showing extensive vascularity within the lesion., Photomicrograph of a surgical specimen showing many intratumoral vessels within the lesion (arrowheads). J Ultrasound Med 2007; 26:
4 Soft Tissue Diffuse Neurofibromas Discussion Diffuse neurofibroma is an uncommon form of neurofibroma that has a uniform matrix of fibrillary collagen that contains Schwann cells, which usually have shorter fusiform contours than those found in conventional neurofibromas. It occurs principally in children and young adults and usually grows slowly, but acceleration of its growth rate has been noted during preg- Figure 4. Soft tissue diffuse neurofibroma in a 28-year-old male patient., Gray scale sonogram showing a large amount of hypoechoic tubular structures within the hyperechoic subcutaneous lesion. Many anechoic ductal structures are visible (arrowheads). Note that the margin between the lesion and the adjacent muscle is poorly defined (arrows)., olor Doppler sonogram showing large (arrowhead) and ectatic (arrow) vessels in the lesion., Photomicrograph of a surgical specimen showing the absence of fat in the lesion. Many large blood vessels are visible within the lesion (arrows). Figure 3. Soft tissue diffuse neurofibroma in an 18-year-old female patient., Extended field-of-view sonogram showing a hyperechoic subcutaneous lesion with a small amount of hypoechoic tubular and nodular structures (arrowheads). The margin between the lesion and the adjacent normal subcutaneous fat is poorly defined (arrows)., olor Doppler sonogram showing only a few vessels within the lesion (arrow)., Photomicrograph of a surgical specimen showing a large amount of fat (arrows) and a small intratumoral vessel (arrowhead). 516 J Ultrasound Med 2007; 26:
5 hen et al nancy and at puberty. diffuse neurofibroma tends to involve the skin and subcutaneous tissues; it is poorly defined and spreads extensively between fat cells and along connective tissue septa, but despite this infiltrative growth pattern, it does not destroy but rather envelops the normal structures it infiltrates, and malignant transformation rarely occurs. Some lesions may consist of large ectatic vessels or prominent mature fat, and this seems to be more common in neurofibromatosis. It is not yet clear how often a diffuse neurofibroma is associated with neurofibromatosis, but it has been suggested that about 10% of patients with this lesion also have neurofibromatosis. 2 lthough sonography has been shown to be highly useful in monitoring soft tissue masses, very little has been reported regarding the utility of sonography in evaluation of soft tissue diffuse neurofibromas. 3,4 In this series, we describe the sonographic morphologic and vascular characteristics of 7 cases. We found that the typical sonographic appearance of soft tissue diffuse neurofibromas was that of a poorly defined subcutaneous hyperechoic mass permeated by multiple irregular hypoechoic tubular or nodular structures. This feature is different from what has previously been reported because the previous 2 reports made no mention of the hyperechoic area. 3,4 When comparing with the described histologic findings, we speculate that our sonographic appearance may be a more accurate description of the pathologic features. The hypoechoic tubular or nodular structures may represent the tumor components of neurofibromatous tissue, whereas the hyperechoic areas may represent the infiltrated subcutaneous fat, the echogenic appearance of which could be explained by the presence of multiple fat/tumor-tissue interfaces. 7 The more the neurofibromatous tissues are present, the more the hypoechoic structures will be seen on sonography. oth previously reported cases showed soft tissue diffuse neurofibromas to be of increased vascularity, 3,4 whereas this characteristic was shown in 5 of our lesions, including multiple ectatic blood vessels in 2 of them; we also found 2 cases with only a few intralesional blood vessels. However, these findings were not correlated well with their histologic findings, in which more blood vessels were seen, although they were small. We speculate that these may relate to the limitation of sonography in detecting tiny vessels with low flow. The location and sonographic appearance of soft tissue diffuse neurofibromas may be confused with those of angiomatous tumors, especially when a patient has no clinical findings of neurofibromatosis. ccording to our limited experience, the brown hyperpigmented skin overlapping the lesion of a diffuse neurofibroma may provide some help in making this distinction because an angiomatous tumor is likely to have purplish red discoloration of the overlying skin. Soft tissue diffuse neurofibromas may also be easily misdiagnosed as soft tissue lipomas or subcutaneous tissue inflammation if they present as hyperechoic-dominant masses. To aid in this differentiation, a lipoma tends to be a hyperechoic mass that contains linear echogenic lines 8 rather than tubular or nodular hypoechoic areas, which are so characteristic of a diffuse neurofibroma. Furthermore, the patient s history and symptom may provide some help in narrowing the differential diagnosis with subcutaneous tissue inflammation. When noninvasive methods fail to provide a definite diagnosis, biopsy may be considered a good method. The magnetic resonance imaging (MRI) appearance of soft tissue diffuse neurofibromas is thought to be characteristic and well correlated with the histologic findings. 9,10 Our study, however, suggests that soft tissue diffuse neurofibromas also have a characteristic sonographic appearance that is well correlated with histologic findings. Given the advantage of being quick, easy to perform, and cost-effective when compared with MRI, sonography should be considered as an alternative imaging modality in the initial evaluation of patients with soft tissue lesions that are presumed to be neurofibromatous. Limitations of sonography include a small field of view, the restricted depth of penetration (especially with high-frequency transducers), and the difficulty in detecting tiny vessels with low flow states. In cases in which the full extent of the lesions is not clear or increased vascularity is not shown on sonography, MRI may be considered for a thorough evaluation. J Ultrasound Med 2007; 26:
6 Soft Tissue Diffuse Neurofibromas In conclusion, our study shows that the sonographic findings of soft tissue diffuse neurofibromas tend to be poorly defined subcutaneous hyperechoic masses with multiple interconnecting hypoechoic tubular or nodular structures and increased vascularity. These findings are characteristic, and sonography should be considered as a useful tool in the initial screening of patients with soft tissue lesions that are presumed to be neurofibromatous. References 1. Murphey MD, Smith WS, Smith SE, Kransdorf MJ, Temple HT. Imaging of musculoskeletal neurogenic tumors: radiologic-pathologic correlation. Radiographics 1999; 19: Enzinger FM, Weiss SW. enign tumors of peripheral nerves. In: Gay SM, Gery L (eds). Soft Tissue Tumors. 3rd ed. New York, NY: V Mosby o; 1995: eggs I, Gilmour HM, Davie RM. Diffuse neurofibroma of the ankle. lin Radiol 1998; 53: hiou HJ, hou YH, hiou SY, Liu J, hang Y. Peripheral nerve lesions: the role of high-resolution US. Radiographics 2003; 23:e Gutmann DH, ylsworth, arey J, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JM 1997; 278: Neurofibromatosis: conference statement National Institutes of Health onsensus Development onference. rch Neurol 1988; 45: ehan M, Kazam E. The echographic characteristics of fatty tissues and tumors. Radiology 1978; 129: huja T, King D, Kew J, King W, Metreweli. Head and neck lipomas: sonographic appearances. JNR m J Neuroradiol 1998; 19: Peh W, Shek TW, Yip DK. Magnetic resonance imaging of subcutaneous diffuse neurofibroma. r J Radiol 1997; 70: Huang GS, Huang W, Lee HS, et al. Diffuse neurofibroma of the arm: MR characteristics. JR m J Roentgenol 2005; 184: J Ultrasound Med 2007; 26:
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