CASE OF THE WEEK PROFESSOR YASSER METWALLY
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1 CLINICAL PICTURE CLINICAL PICTURE: A 22 years old male patient presented clinically with bilateral tinnitus, headache, bilateral diminution of hearing, bilateral papilledema, bilateral facial nerve palsy, bulbar cranial nerves dysfunction, right sided cerebellar manifestation and bilateral long tract dysfunction. RADIOLOGICAL FINDINGS RADIOLOGICAL FINDINGS: CASE OF THE WEEK PROFESSOR YASSER METWALLY Figure 1. Bilateral vestibular schwannomas. The bilateral cerebellopontine angle tumors are hypointense on the precontrast MRI T1 images (Antoni B schwannomas). Notice that the brain stem is bilaterally compressed and squeezed by the bilateral tumors. Also notice the CSF cleft that separates the bilateral tumors from the neural tissues (The tumors are extra-axial). Moderate degree of hydrocephalus is present.
2 Figure 2. Bilateral vestibular schwannomas. Postcontrast MRI T1 images showing dense and uniform contrast enhancement of the bilateral tumors. Figure 3. Bilateral vestibular schwannomas. MRI T2 and FLAIR images. The tumors have heterogenous signal on both T2 and FLAIR images with hyperintense zones which, most probably, represent cystic (fluid -filled) areas (Antoni B tissues).
3 Figure 4. Bilateral vestibular schwannomas. MRI FLAIR images. Notice the moderate hydrocephalic changes and the transependymal edema. Also notice the CSF cleft that separates the tumor from the brain stem. The tumor hyperintensity is due to the existence of cystic changes (Antoni B tissues). Figure 5. Bilateral vestibular Antoni B tissue schwannoma. Notice that the tumours are hypointense of precontrast MRI T1 image, with intense contrast enhancement. The tumours are mainly hyperintense in MRI T2 image. Notice the CSF cleft that separate the tumours from the brain stem,a sign which indicates the extraaxial location of the tumours. The brain stem is compressed bilaterally. The T1,T2 signal changes are due to the higher water content of Antoni B tissue.
4 DIAGNOSIS: DIAGNOSIS: NEUROFIBROMATOSIS TYPE 2 Synonyms: DISCUSSION DISCUSSION: Bilateral acoustic neurofibromatosis Bilateral vestibular schwannomas (Antoni B schwannomas, surgically confirmed) Benign nerve sheath tumors can be categorized into schwannoma and neurofibroma based on histopathologic characteristics. Schwannomas are solitary encapsulated tumors located along cranial or spinal nerves or nerve roots. These tumors consist of Schwann cells and do not contain nerve tissue. Histologically the tumor contains a mixture of two clear-cut patterns: Antoni A tissue has a compact arrangement of cells and reticulin fibers. Antoni B tissue is loose textured, mucinous, and free of fibrillary background. These lesions can be seen in association with neurofibromatosis. Figure 6. Antoni A tissue [a] and Antoni B tissues [b] Figure 7. A, Schwannoma. B, A schwannoma with mixed Antoni A, dense cellular areas, and Antoni B, loosely structured areas. TISSUE TYPE DESCRIPTION It consists of compact bipolar, elongated, spindle-shaped, lipid rich schwann cells with twisted nuclei, indistinct cytoplasmic borders, and, occasionally,
5 Antoni A tissue (Dense, fibrillary, solid compact type) Antoni B tissue (Loose, reticulated, cystic type) clear intranuclear vacuoles. The cells are arranged in short bundles or interlacing fascicles with nuclear palisading, whorling of the cells, and Verocay bodies. Verocay bodies are formed by 2 compact rows of wellaligned nuclei and cell processes that are arranged in a roughly oval shape. Is loose textured, mucinous and free of fibrillary background. Cells are separated by large amount of oedematous tissue that coalesce to form cystic spaces. Cells are scanty and vacuolated Neurofibromas are tumors of the cranial, spinal, or peripheral nerves and are intimately continuous with the nerve proper. The affected nerve is circumferentially compressed and diffusely penetrated by elements of tumor. Histopathologically neurofibromas contain all elements of the nerve, including Schwann cells, myelinated and unmyelinated nerve fibers, and fibroblasts. Thus it is difficult to remove the tumor without sacrificing the nerve. Plexiform neurofibromas are pathognomonic of von Recklinghausen's disease. These tumors appear as tortuous entanglements or fusiform enlargements of the peripheral nerves. They often trap soft tissues, such as adipose tissue and muscle. Malignant nerve sheath tumors are seen in association with neurofibromatosis. Figure 8. Schwannoma, A, and neurofibroma, B Figure 9. A, Schwannoma. Antoni A, densely cellular area, no Verocay body. B Schwannoma. Antoni A, densely cellular area with nuclear palisading or Verocay body Pathologically neurofibromas are composed of a central fibrocollagenous core and a peripheral myxomatous tissues. These tissue characteristics frequently determines the MRI appearance of neurofibromas.
6 Figure 10. The peripheral myxomatous tissue (yellow) and the central fibrocollagenous core of neurofibromas (brown) Schwannomas Usually single tumours (only multiple in type II neurofibromatosis,bilateral acoustic schwannomas) Composed of schwann cells only Antoni A,B, tissues Neurofibromas Invariably multiple Composed of all nerve tissues (schwann cells, myelinated and nonmyelinated nerve tissues and nerve axons) The loose, myxomatous Antoni type B tissue of a neurilemoma may mimic a neurofibroma. However, NFs lack the thick collagenous capsule of a neurilemoma and instead are surrounded by a variably thickened perineurium and epineurium. NFs also lack the Antoni type A and B patterns, as well as Verocay bodies, typical of a neurilemoma. NFs are composed of a mucinous matrix containing scattered myelinated and nonmyelinated axons along with a heterogeneous cell population including Schwann cells, fibroblasts and perineural cells. Immunoreactivity for S- 100 protein consequently is observed in only a portion of the cells comprising a NF, as opposed to uniform reactivity throughout a neurilemoma. CT SCAN IMAGING OF NERVE SHEATH TUMOURS CT-Pathology correlation of schwannomas Cell type Schwannomas with Antoni A tissue Schwannomas with Antoni B tissue CT scan picture Schwannomas with Antoni A tissue containing lipid- rich Schwann cells appear lucent on noncontrast CT scan. Schwannomas with Antoni B tissue appear cystic on CT scan as a result of loosely textured stroma that has a cystic component. The cells are separated by large amounts of edematous fluid, which coalesce to form cystic spaces. Cystic changes are more common in the cranial schwannomas than in spinal lesions (Antoni B schwannomas are more common intracranially)
7 Figure 11. A, Postcontrast CT showing bilateral vestibular schwannomas. Notice central cavitations (Antoni B tissues), B, postmortem specimen showing vestibular schwannoma compressing the brain stem. Figure 12. A. showing the cystic Antoni B schwannoma compressing the brain stem, B, showing the solid neurofibroma Figure 13. A, Vestibular schwannoma (arrows). B, Histologically, the tumor is made up of sheets of uniform spindle cells, some of which are forming palisades called Verocay bodies.
8 Figure 14. The sheets of uniform spindle cells resemble normal Schwann cells. In addition, a foamy, reticulated tissue is sometimes seen in these tumors, which may represent degeneration of these cells. The dense spindled areas are known as Antoni A areas while the looser areas are Antoni B. Both types of tissue are seen in this figure. CT-Pathology correlation of neurofibroma Neurofibromas with predominantly lipid- rich Schwann cells are lucent on CT scan. Neurofibromas composed predominantly of compactly arranged collections of fibroblasts with abundant production of dense bundles of collagen appear dense on CT scan. Tumors show minimal to intense, homogeneous to inhomogeneous, or peripheral ringlike enhancement on postcontrast study. MRI IMAGING OF NERVE SHEATH TUMOURS Imaging of schwannomas Schwannomas arise from perineural Schwann cells. They are neoplasms that usually arise from sensory nerves. In the intracranial compartment, approximately 80% of schwannomas involve the internal auditory canal. Bilateral acoustic schwannomas are diagnostic of neurofibromatosis type 2. 1 Figure 15. Schwannoma. Antoni B, loosely cellular areas with vacuolated cells and with round or oval nuclei.
9 Figure 16. Foramen magnum schwannoma. A, Contiguous off-midline sagittal unenhanced Tl- weighted MR images demonstrate a circumscribed mass (arrows) at the foramen magnum. B, Coronal enhanced Tl -weighted MR image shows avid enhancement of the schwannoma. Note central hypointensity consistent with necrosis (arrowhead), widening of the ipsilateral cerebrospinal fluid (CSF) space (arrows), and displacement of the cervicomedullary junction from right to left. Calcification and reaction in the adjacent bone are unusual. The MR imaging appearance of schwannomas is dependent on their cellular makeup. Antoni type A tumors are composed of packed cells, resulting in a hypointense appearance (isointense to brain) on T2-weighted imaging. Antoni type B schwannomas typically have a higher water content and a low cell ratio resulting in a hyperintense appearance on T2-weighted imaging. 2 A given acoustic neuroma may contain areas Antoni type A tumors are composed of packed cells, resulting in a hypointense appearance (isointense to brain) on T2-weighted imaging. Antoni type B schwannomas typically have a higher water content and a low cell ratio resulting in a hyperintense appearance on T2-weighted imaging. with both Antoni A and Antoni B tissue. Most schwannomas enhance; however, the enhancement is frequently heterogeneous. 3 This is largely related to the development of central necrosis, which occurs in most lesions that are more than 2 cm in size. The presence of an enhancing dural tail is unusual with schwannomas, but may occasionally be present. Figure 17. Antony B schwannoma Cell type Antoni type A schwannomas (solid hypercellular tumours with high nuclear to cytoplasmic ratio and with minimal extracellular water) MRI picture The tumours are composed of packed cells, resulting in a hypointense appearance (isointense to brain) on T2- weighted imaging.
10 Antoni type B schwannomas (cystic tumours) The tumours typically have a higher water content and a low cell ratio resulting in a hyperintense appearance on T2-weighted imaging. The other common region in the posterior fossa where extra-axial neoplasms occur is the cerebellopontine angle. Enhancing masses that occur in the cerebellopontine angle in decreasing order of frequency include schwannomas, meningiomas, and metastatic disease. 2 Other lesions that may occur here include aneurysms arising from the anterior inferior cerebellar artery or the vertebral-basilar system. 2 Exophytic brainstem gliomas and fourth ventricular ependymomas may extend into the cerebellopontine angle and foramen magnum, 2 but the origin of these masses from the brain- stem and fourth ventricle, respectively, is usually evident. Schwannomas in the cerebellopontine angle arise in most cases from cranial nerve 8 (the vestibular division is more common than cochlear nerve). The next most common nerves of origin are cranial nerve 5 (trigeminal) followed by cranial nerve 7 (facial). Several imaging findings may help to distinguish a schwannoma from a meningioma in the cerebellopontine angle. Schwannomas involve the internal auditory canal in approximately 80% of cases, compared with meningiomas where involvement of the internal auditory canal is unusual, seen in approximately 5% of cases. Schwannomas make an acute angle with the petrous bone, compared with meningiomas, which make obtuse angles owing to their dural origin. Because schwannomas extend into the internal auditory canal, when large enough, there may be flaring or expansion of the porus acousticus (the opening of the internal auditory canal) as well as the canal itself. With schwannomas, there is frequently obscuration of the seventh and eighth nerves, compared with meningiomas in which these nerves often can be seen separate from the tumor on imaging. 2 In addition, in approximately 10% of cases, schwannomas may be associated with a coexistent arachnoid cyst. Finally, although schwannomas usually are centered geographically at the internal auditory canal, meningiomas frequently are centered anterior or posterior and superior or inferior to it. Schwannomas involve the internal auditory canal in approximately 80% of cases, compared with meningiomas where involvement of the internal auditory canal is unusual, seen in approximately 5% of cases. Schwannomas make an acute angle with the petrous bone, compared with meningiomas, which make obtuse angles owing to their dural origin. Because schwannomas extend into the internal auditory canal, when large enough, there may be flaring or expansion of the porus acousticus (the opening of the internal auditory canal) as well as the canal itself. With schwannomas, there is frequently obscuration of the seventh and eighth nerves, compared with meningiomas in which these nerves often can be seen separate from the tumor on imaging. 5 In 10% of cases, schwannomas may be associated with a coexistent arachnoid cyst. Although schwannomas usually are centered geographically at the internal auditory canal, meningiomas frequently are centered anterior or posterior and superior or inferior to it. Metastases involving the cerebellopontine angle are typically dural based, en plaque lesions, caused by hematogenous spread, subarachnoid seeding along the cranial nerves, or extension from an adjacent bone lesion. Common metastases to affect the cerebellopontine angle include breast, lung, and prostate carcinoma, as well as lymphoma. In the pediatric population, leukemia and neuroblastoma should be considered. Figure 18. Bilateral vestibular schwannoma with intense contrast enhancement.
11 Figure 19. A,B Left cerebellopontine angle schwannoma in a middle-aged man. A, Axial T2-weighted MR image obtained at the level of the internal auditory canals. There is a heterogeneous, predominantly hypointense mass within the left cerebellopontine angle. Central high signal intensity is consistent with necrosis. Note the CSF cleft (black arrows) separating this extra-axial mass from the adjacent brainstem and cerebellum. There is widening of the internal auditory canal (white arrowheads). B, Axial enhanced Tl -weighted MR image demonstrates heterogeneous enhancement of the mass. Enhancement extends into the opening of the internal auditory canal. In addition, there are small enhancing dural tails (arrows). C, Cerebellopontine cistern epidermoid cyst. Axial unenhanced T1 -weighted image shows the mass conforming to the shape of the cerebellopontine cistern. The basilar artery is encased (white arrow), and the posterior margin of the cyst is scalloped (black arrows). Figure 20. A, small acoustic neuroma within the internal auditory canal is easily seen on postgadolinium MRI. B, MRI T2 image showing bilateral vestibular Antoni B tissue schwannoma, the tumours are hyperintense.
12 Figure 21. Precontrast MRI T1 (A) and postcontrast MRI T1 (B) images showing a case with type II neurofibromatosis (bilateral acoustic schwannomas). The tumours are hypointense on the precontrast MRI T1 image (A) with intense and uniform postcontrast enhancement (B). Notice the clear CSF cleft that separated the tumours from the brain stem, indicating the extraaxial nature of the tumours that are seen compressing the brain stem bilaterally. C, The tumours were surgically removed with the histopathological diagnosis of Antoni B schwannomas. Imaging of neurofibromas Benign nerve sheath tumors are isointense to slightly hyperintense to muscle in TI-weighted pulse sequences. These tumors show variable hyperintensity in T2-weighted images; Varma et al 4 have demonstrated a target sign (a peripheral hyperintense rim and a central low intensity) in T2-weighted sequences. This target pattern is attributed to peripheral myxomatous tissue and central fibrocollagenous tissue. This pattern was absent in lesions with cystic, hemorrhagic, or necrotic degeneration.
13 Figure 22. Neurofibroma. These peripheral nerve tumors resemble Schwannomas and are differentiated from the latter by histological criteria that are not always distinct. As a rule, however, neurofibromas are less cellular, lack striking palisading, are more loosely packed than Schwannomas, and may have a much more striking collagenous component (red bundles). A target sign was not seen in malignant lesions. A mass with a target appearance if seen by MR imaging is a useful sign in diagnosis of benign nerve sheath tumors. This sign is seen in both neurofibromas and schwannomas. Neither CT nor MR imaging can always accurately differentiate benign from malignant nerve sheath tumors. If masses are seen with irregular contour and disruption of soft tissue planes, however, findings favor malignant neoplasm. Figure 23. MRI picture of the target sign Spinal schwannoma & neurofibromas Schwannomas and neurofibromas typically involve the dorsal sensory nerve roots. Depending upon their site of origin, they can be intradural, extradural, or both, forming a "dumbbell" or hour-glass shaped mass. Rarely, schwannomas may extend into the substance of the spinal cord and be entirely intramedullary in location. Plain radiographs may show an enlarged neural foramen or spinal canal. There may be associated findings of neurofibromatosis (scoliosis, vertebral dysplasia). CT-myelography will show the bony changes if present and an intradural, extramedullary mass with rounded, well-defined margins. Schwannomas appear iso- to hypointense relative to spinal cord on TI-weighted images and hyperintense on T2-weighted images (cystic Antoni B schwannoma). Areas of even greater signal hyperintensity on T2-weighted images may represent cyst formation; conversely, areas of relatively decreased signal intensity on T2-weighted images may relate to intratumoral hemorrhage, dense cellularity, or collagen deposition. The tendency for cyst formation is greater in spinal tumors than in intracranial lesions. In contrast, neurofibroma is a solid tumor; cystic areas are uncommon. They have more uniform signal intensity on MR images, in keeping with their more uniform histologic appearance on the T2-weighted images, a target appearance may be seen with relatively greater signal intensity peripherally, corresponding to peripheral myxomatous tissue and central fibrocollagenous tissue seen histologically. Contrast- enhanced MR imaging may show a central area of decreased signal intensity surrounded by enhancing tumor in either neurofibroma or schwannoma.
14 Figure 24. MRI T2 images showing a dumb-bell neurofibroma notice the T2 hypointensity (B) which could be due to intralesional haemorrhage,, dense cellularity, or collagen deposition These tumors show variable hyperintensity in T2-weighted images;the target sign is occasionally demonstrated (a peripheral hyperintense rim and a central low intensity) in T2-weighted sequences This target pattern is attributed to peripheral myxomatous tissue and central fibrocollagenous tissue. This pattern is absent in lesions with cystic, hemorrhagic, or necrotic degeneration. Figure 25. MRI T2 images showing the target sign,with central hypointensity corresponding to the fibrocollagenous core and a peripheral hyperintensity corresponding to the peripheral myxomatous tissue Plexiform neurofibroma is a distinct lesion that is characteristic of NFl. Although these are infiltrative lesions that occur most commonly near the orbital apex or superior orbital fissure, they can occur anywhere in the body. On MR imaging, the lesions appear hypointense relative to cord on TI-weighted images and hyperintense on T2-weighted images with variable contrast enhancement. SUMMARY SUMMARY Central neurofibromatosis or NF type 2 is a multisystem genetic disorder associated with bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas, gliomas, and juvenile cataracts with a paucity of cutaneous features, which are seen more consistently in NF1. Although quite variable in its age of onset and severity of symptoms in affected individuals, NF2 is associated with significant morbidity and decreased lifespan. Furthermore, diagnosis in childhood is often difficult because of the absence of central nervous system involvement at a young age. Table 1. Genetics of neurofibromatosis Type Gene product Gene location Gene function
15 Type I neurofibromatosis Neurofibromin Long arm of chromosome 17 Putative tumor suppressor function Type II neurofibromatosis Merlin Long arm of chromosome 22 Addendum A new version of this PDF file (with a new case) is uploaded in my web site every week (every Saturday and remains available till Friday.) To download the current version follow the link " You can also download the current version from my web site at " To download the software version of the publication (crow.exe) follow the link: The case is also presented as a short case in PDF format, to download the short case follow the link: At the end of each year, all the publications are compiled on a single CD-ROM, please contact the author to know more details. Screen resolution is better set at 1024*768 pixel screen area for optimum display. For an archive of the previously reported cases go to then under pages in the right panel, scroll down and click on the text entry "downloadable case records in PDF format" REFERENCES References 1. Spagnoli MV, Goldberg HI, Grossman RI, et al: Intracranial meningiomas: High-field MR imaging. Radiology 161: , Press GA, Hesselink JR: MR imaging of cerebellopontine angle and internal auditory canal lesions at 1.5T. AJNR Am j Neuroradiol 9: , Nguyen HD, Simonson TM, Fisher DJ, et al: MR evaluation of acoustic schwannoma with fractional contrast doses. J Comput Assist Tomogr 19:23-27, Varma DGK, Moulopoulos A, Sara AS, et al: MR imaging of extracranial nerve sheath tumors. j Comput Assist Tomogr 16:448, Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008
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