DOI: 10.1148/rg.24si035170
RadioGraphics 2004;24:S237-S242
© RSNA, 2004
LOWER GENITOURINARY TRACT IMAGING |
Best Cases from the AFIP
Plexiform Neurofibroma of the Bladder1
Lana M. Wilkinson, MD,
David Manson, MD, FRCPC and
Charles R. Smith, MD, FRCPC
1 From the Department of Medical Imaging, Hospital for Sick Children, Toronto, Ontario, Canada. Received July 22, 2003; revision requested August 18 and received September 24; accepted September 25. All authors have no financial relationships to disclose. Address correspondence to L.M.W., 1330 West Ave, #3005, Miami Beach, FL 33139 (e-mail: wilkinlm@hotmail.com).
Index Terms: Bladder neoplasms, 83.3199 • Nerves, neoplasms, 83.3199 • Neurofibromatosis, 83.18 • Neuroma, 83.3199
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History
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An 18-year-old man with an established history of neurofibromatosis type 1 (NF1) presented with weight loss and umbilical protrusion. He denied any pain, urinary symptoms, or gastrointestinal symptoms. An initial ultrasound (US) examination of the abdomen and pelvis demonstrated bilateral hydronephrosis and bladder wall thickening, which led to urologic consultation and, ultimately, cystoscopy. At cystoscopy, the bladder mucosa was noted to be irregular and compressed, but no focal intraluminal mass was appreciated. There was some apparent difficulty in identifying the ureteral orifices.
Further imaging with computed tomography (CT) and magnetic resonance (MR) imaging showed a large mass involving the bladder wall and causing the hydronephrosis. Bilateral nephrostomy tubes and ureteric stents were placed in an antegrade fashion, which succeeded in relieving the urinary obstruction. Subsequently, the nephrostomy tubes were removed and the ureteric stents were left in place. The patient underwent a surgical biopsy, which demonstrated pathologic changes diagnostic of neurofibroma. The possibility of malignant degeneration was considered given the size of the mass, resulting in the referral of the patient to a tertiary-care center for radical cystectomy and urinary diversion.
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Imaging Findings
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Initial CT performed with intravenous and rectal contrast material showed a large mass nearly encasing the bladder and causing bilateral ureterovesical junction obstruction. The mass appeared heterogeneous but predominantly hypoattenuating and measured approximately 10 x 10 x 18 cm. The lumen of the bladder was displaced anterosuperiorly to the right (Fig 1).
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Figure 1a. Axial delayed CT scans obtained with intravenous and rectal contrast material show hydronephrosis (a), which was secondary to a large predominantly hypoattenuating mass in the bladder wall (b).
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Figure 1b. Axial delayed CT scans obtained with intravenous and rectal contrast material show hydronephrosis (a), which was secondary to a large predominantly hypoattenuating mass in the bladder wall (b).
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MR imaging was performed, which again showed the large bladder mass and the secondary hydronephrosis. The mass was heterogeneous in signal intensity but had predominantly low signal intensity on T1-weighted images and high signal intensity on T2-weighted images (Fig 2). The target sign was demonstrated best on the T2-weighted images, making the diagnosis of plexiform neurofibroma more likely (Fig 3). The target sign is seen as relatively low signal intensity centrally with relatively high signal intensity peripherally and is very suggestive of neurofibroma, in this case the plexiform variety. There was mild nonuniform enhancement after administration of gadolinium contrast material (Fig 4).
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Figure 3a. Sagittal (a) and axial (b) T2-weighted MR images show that the mass contains multiple areas of low signal intensity centrally and high signal intensity peripherally (arrow in a). This finding is referred to as the target sign and is suggestive of plexiform neurofibroma.
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Figure 3b. Sagittal (a) and axial (b) T2-weighted MR images show that the mass contains multiple areas of low signal intensity centrally and high signal intensity peripherally (arrow in a). This finding is referred to as the target sign and is suggestive of plexiform neurofibroma.
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Pathologic Evaluation
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The preoperative diagnosis was ganglioneuroma and therefore consideration was given to removal of the lesion. However, intraoperative diagnosis of plexiform neurofibroma was made by means of frozen sectioning; because of the ubiquitous nature of this disorder, no attempt was made to achieve complete removal.
The tumor weighed 1,225 g and measured 31 (vertical) x 14 (coronal) x 9 (sagittal) cm. It involved and distorted the entire bladder, extending inferiorly to the prostate gland. The tumor was composed of masses of soft, fleshy nodules, varying in size up to 1.5 cm in diameter (Fig 5). It was surrounded by a thin, fibrous pseudocapsule. No wormlike ("plexiform") expansions of nerves were apparent.
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Figure 5. Horizontally oriented cross section of the tumor shows the bladder mucosa (M) surrounded by masses of nodules. Arrows = locations of the ureteric orifices. (Scale is in centimeters.)
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The microscopic appearance was typical of a plexiform-type neurofibroma, in which some cells lay in a pattern reminiscent of normal nerve (Fig 6a). A more disorganized arrangement predominated, wherein the randomly oriented fibers expanded and distorted the few identifiable nerves (Fig 6b). The lesion was not encapsulated. The tumor surrounded but did not invade the ureters, nor did it invade the structures of the spermatic cord; similarly, it abutted the bladder mucosa but did not invade it. No mitotic activity or other evidence of malignancy was present.
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Figure 6a. (a) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows that the oval plexiform neurofibroma (PNF) has a denser outer core with areas that have a looser configuration. It is surrounded by fibrous tissue and pushes aside elongated smooth muscle cells (SM). (b) Photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows that the plexiform neurofibroma (PNF) has variable architecture. On the right, the tumor cells have a wavy, parallel arrangement; on the left, the cells are arranged more loosely and haphazardly. There is no true capsule. The tumor pushes aside bundles of smooth muscle cells (SM).
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Figure 6b. (a) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows that the oval plexiform neurofibroma (PNF) has a denser outer core with areas that have a looser configuration. It is surrounded by fibrous tissue and pushes aside elongated smooth muscle cells (SM). (b) Photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows that the plexiform neurofibroma (PNF) has variable architecture. On the right, the tumor cells have a wavy, parallel arrangement; on the left, the cells are arranged more loosely and haphazardly. There is no true capsule. The tumor pushes aside bundles of smooth muscle cells (SM).
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Discussion
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Neurofibromatosis type 1 (NF1) is an inherited disorder that predominantly affects the skin and peripheral nervous system. Transmission is autosomal dominant, with the genetic abnormality localized to the long arm of chromosome 17. The condition has a high penetrance but variable phenotypic expression. There is a very high spontaneous mutation rate, with at least 50% of cases related to new mutations (1). NF1 is a very common genetic disease, with a prevalence of approximately 1 in 3,000. The syndrome is more common in males, with a male-female ratio of 3:1.
NF1 is primarily a disorder of neural crest derivation; however, tissues typically considered mesodermal in origin are also affected. The diagnosis can be made if two or more of the following are present: (a) six or more café au lait spots, (b) two or more neurofibromas, (c) one or more plexiform neurofibromas, (d) freckling in the axilla or inguinal region, (e) optic glioma, (f) two or more Lisch nodules, (g) a distinctive osseous lesion, or (h) a first-degree relative with NF1 (2). The diagnosis is usually suspected in childhood when café au lait spots are identified. Cutaneous tumors, a classic finding of the disease, are seen in only 40% of those with the condition and often do not manifest until after puberty (3). Associated conditions include seizures, developmental delay, focal gigantism, and endocrine dysfunction.
Neurofibromas are composed of nerve sheath cells interspersed with collagen bundles and show varying degrees of myxoid degeneration. They are unencapsulated and show no clear division between Antoni A and B areas within the tumor. Nerve fibers run through a neurofibroma as opposed to a schwannoma, where nerve fibers travel around the tumor. This feature makes excision more difficult and nerve damage a more likely possibility.
Neurofibromas can be subclassified into three groups: (a) localized, (b) diffuse, and (c) plexiform (4). The localized neurofibroma is typically painless, slow growing, and less than 5 cm in diameter. Most of these are solitary lesions and not associated with the NF1 syndrome. Diffuse neurofibromas are poorly defined, infiltrative lesions in the subcutaneous fat seen in children and young adults. They are generally solitary lesions as well and similarly not related to any inherited condition.
In contrast, plexiform neurofibromas are usually seen in patients with NF1, and if seen in combination with multiple localized neurofibromas, are virtually pathognomonic for NF1. Plexiform neurofibromas show diffuse involvement along a nerve and its branches. The gross enlargement of the nerve with nodular tumor development has resulted in the gross pathologic appearance referred to as a "bag of worms." The tumor is often disfiguring and affects function due to sheer size as well as neurovascular compromise. In patients with NF1, the localized neurofibroma is the most common type encountered. However, when seen in this setting, they tend to be larger than sporadic localized neurofibromas, to be multiple, and to involve deep nerves.
Neurofibroma of the genitourinary tract is relatively rare, with only 75 cases reported in the literature, to our knowledge (5). In general, patients with involvement of the genitourinary tract have other manifestations of NF1. Although patients may present with a number of symptoms, urinary tract infection is the most common clinical manifestation, seen as the presenting symptom in almost two-thirds of patients (6). Urinary retention, frequency, urgency, hematuria, and a pelvic mass are other manifestations of genitourinary involvement. The majority of patients have hydronephrosis, decreased bladder capacity or compliance, and a thickened bladder wall (5). Neurofibromas appear to be derived from the pelvic, vesical, and/or prostatic nerve plexuses, which form a continuous network, allowing the plexiform neurofibroma to spread and involve multiple organs.
Neurofibromas can be visualized with many imaging modalities. US is often the initial investigation, especially in children. Neurofibromas appear as solid, round or oval masses that are relatively nonspecific and may look very similar to a leiomyoma. Bladder involvement can manifest as a focal mass or diffuse bladder wall thickening in the case of a plexiform neurofibroma. However, CT and MR imaging are often needed to further characterize the abnormality and to better define the extent of tumor involvement.
At CT, neurofibromas are round or oval, well-defined, homogeneous masses that have an attenuation value of 20–25 HU on nonenhanced scans and 30–50 HU after contrast material administration. It is thought that one of the best imaging features for diagnosis is a fusiform mass, which represents the nerve entering and exiting the tumor (4). The low attenuation is attributed to high lipid or water content within the mucinous matrix, entrapment of perineural adipose tissue, and less often cystic degeneration (7).
At MR imaging, neurofibromas generally have homogeneous low signal intensity on T1-weighted images and homogeneous high signal intensity (higher than fat) on T2-weighted images. Relatively homogeneous enhancement is seen after administration of gadolinium contrast material. The target sign is a more specific sign of a neurogenic tumor, in particular a neurofibroma, as has been described in the literature (8). This sign correlates well with the pathologic findings of peripheral nerve sheath tumors. The target sign, best seen on T2-weighted images, is described as low signal intensity centrally with a ring of high signal intensity peripherally.
On T1-weighted images, the reverse is true, with the center demonstrating a higher signal intensity than the periphery. At pathologic analysis, this sign represents a central core made up of collagenous and fibrillary tissue with peripheral less densely cellular myxoid tissue (9). Myxoid stroma enhances, helping differentiate the high signal intensity at T2-weighted imaging from cystic change or necrosis (8). Plexiform neurofibromas commonly show the target sign; however, the mass will be larger and more infiltrating with lobulated borders and show inhomogeneous enhancement. The case presented demonstrates this target sign in a large plexiform neurofibroma of the bladder.
Malignant degeneration is estimated to occur in approximately 5% of patients with NF1 (4). It occurs more commonly in the plexiform variety. Malignant peripheral nerve sheath tumors can look identical to their benign counterparts, but progressive enlargement and pain related to the mass are suggestive findings. In addition, irregular infiltrative borders and internal inhomogeneity at imaging should raise the possibility of malignant degeneration.
The differential diagnosis for a large mass involving the bladder with extension into surrounding structures includes rhabdomyosarcoma, ganglioneuroma, and retroperitoneal fibrosis (10). In a patient with a history of NF1, the primary consideration should be a plexiform neurofibroma.
Treatment of patients with NF1 and bladder involvement is not standard and depends on the extent of disease, the symptoms, and suspicion for malignant degeneration. In general, management is conservative unless there are intractable symptoms such as hydronephrosis, severe bladder volume loss, or increasing size of the tumor. Unfortunately, chemotherapy and radiation have shown no success in the treatment of these lesions. Often, radical cystectomy with urinary diversion is necessary. Recurrence is common, as it is difficult to resect the entire tumor.
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Summary
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Neurofibromas are common benign peripheral nerve sheath tumors. Multiple solitary neurofibromas and plexiform neurofibromas are seen in NF1. The imaging appearance of fusiform enlargement of a nerve suggests the solitary variety, and a larger, lobulated, "bag of worms" appearance suggests the plexiform variety. The more specific target sign seen on T2-weighted images correlates with the pathologic appearance of a central core made up of collagen and fibrous tissue and a periphery of less cellular myxoid tissue. Genitourinary involvement is not common; however, in a patient with a history of NF1 and a mass involving the bladder that shows the target sign at MR imaging, this diagnosis is the top consideration. Malignant degeneration, although rare, should be suspected in masses associated with increasing size, irregular borders, and pain referable to the mass. Treatment of patients with neurofibromatosis involving the bladder often involves radical cystectomy with urinary diversion, as was the case for our patient. Symptoms of urinary obstruction or concern about malignant degeneration often make this necessary.
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Footnotes
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Abbreviation: NF1 = neurofibromatosis type 1
Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
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References
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- Holt JF. Neurofibromatosis in children. AJR Am J Roentgenol 1978; 130:615-639.[Medline]
- Mulvihill JJ, Parry DM, Sherman JL, Pikus A, Kaiser-Kupfer MI, Eldridge R. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis): an update. Ann Intern Med 1990; 113:39-52.
- Brasfield RD, DasGupta TK. Von Recklinghausen’s disease of the bladder: a clinicopathological study. Ann Surg 1972; 175:86-104.[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]
- Nguyen HT, Kogan BA, Hricak H, Turzan C. Plexiform neurofibroma involving the genitourinary tract in children: case reports and review of the literature. Urology 1997; 49:257-260.[CrossRef][Medline]
- Shonnard KM, Jelinek JS, Benedikt RA, Kransdorf MJ. CT and MR of neurofibromatosis of the bladder. J Comput Assist Tomogr 1992; 16:433-438.[Medline]
- Bass JC, Korobkin M, Francis IR, Ellis JH, Cohan RH. Retroperitoneal plexiform neurofibromas: CT findings. AJR Am J Roentgenol 1994; 163:617-620.[Abstract/Free Full Text]
- Nishimura H, Zhang Y, Kazuaki O, Masafumi U, Naofumi H, Shiliang S. MR imaging of soft-tissue masses of the extraperitoneal spaces. RadioGraphics 2001; 21:1141-1154.[Abstract/Free Full Text]
- Suh JS, Abenoza P, Galloway HR, Everson LI, Griffiths HJ. Peripheral (extracranial) nerve tumors: correlation of MR imaging and histologic findings. Radiology 1992; 183:341-346.[Abstract/Free Full Text]
- Smirniotopoulos JG, Lonergan GJ, Abbott RM, et al. Image Interpretation Session: 1998. RadioGraphics 1999; 19:205-233.[Free Full Text]
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