Neurogenous Tumors and Neurofibromatosis Affecting Bone

Radiologic Features

The classic radiologic presentation of meningioma is that of a homogeneously contrast enhancing dura-based mass with small peripheral extensions referred to as the dural tail ( Fig. 14-3 ). Other radiographic presentations include a flattened extensive lesion referred to as en plaque meningioma or an intraventricular (choroid plexus) meningioma. In addition, classic presentation is as a very large anterior cranial fossa mass centered in the midline (olfactory groove meningioma) ( Fig. 14-3 ). Meningioma may also present as a purely intraosseous tumor. In such instances, it may be mistaken for a different type of primary bone lesion; for example, intraosseous meningioma of the sphenoid bone may be mistaken for fibrous dysplasia. In addition, some histologic subtypes of meningioma may contribute to misdiagnosis; for example, intraosseous secretory meningioma may be mistaken for metastatic carcinoma ( Fig. 14-4 ).

Some meningiomas show involvement of three anatomic compartments: cranial bone, intracranial extension, and extracranial extension into the scalp ( Fig. 14-5 ). Often, meningiomas induce prominent periosteal new bone formation in the form of perpendicular striations that radiate from the lesion on the inner and outer surfaces of the affected bone ( Fig. 14-6 ). Meningiomas must therefore be differentiated radiographically from other primary and metastatic bone lesions. Higher grade meningiomas frequently exhibit atypical radiographic features as well, including a blurred or diffuse interface with the subjacent brain parenchyma, or a multilobulated appearance (mushroom sign). In addition, brain invasive meningiomas are often accompanied by marked brain edema ( Fig. 14-7 ).

Microscopic Findings

Microscopically, meningiomas represent a group of neoplasms with various heterogenous features linked by focal similarities to normal meningothelial cells ( Table 14-1 ). The nuclei are round or oval with small nucleoli and fine, evenly dispersed chromatin. Intranuclear inclusions are frequently present. The four classic histologic subtypes of meningioma are syncytial, fibroblastic, transitional, and psammomatous ( Fig. 14-8 ).

Syncytial meningioma is characterized by patternless architecture, without other distinctive features. The lack of a distinct cytoplasmic border (i.e., the syncytial appearance of meningothelial cells) is explained at the ultrastructural level by the complex interdigitating cytoplasmic processes.

Fibroblastic or spindle-cell meningioma is characterized by the presence of elongated spindle cells arranged in fascicles with a focal storiform pattern. Focal syncytial features with a whorled pattern and psammoma bodies are present in some fibroblastic meningiomas.

Transitional meningioma shows the presence of clearly recognizable syncytial areas and fibroblastic features. Cellular whorls are typical for this type, which is also known as mixed meningioma.

Psammomatous meningioma is characterized by prominent numbers of calcifications with a concentrically layered architecture referred to as psammoma bodies. Scattered psammoma bodies can be seen in virtually any subtype of meningioma; however, they are, by definition, particularly abundant and densely packed in the psammomatous variant.

Angiomatous meningioma is characterized by prominent vascularity. The outdated term angioblastic meningioma encompassed at least three different types of tumor, including angiomatous meningioma, hemangiopericytoma, and hemangioblastoma, which are considered distinctly different neoplasms today. The morphologic features frequently overlap with those of microcystic meningioma ( Fig. 14-9 ).

Metaplastic meningioma exhibits focal areas of metaplasia, which may differentiate along cartilaginous, osseous, or lipomatous lines. There is no prognostic significance ( Fig. 14-9 ).

Secretory meningioma has microscopic features similar to those of syncytial or transitional meningioma. In addition, individual tumor cells show discrete intracytoplasmic inclusion bodies that are strongly positive for carcinoembryonic antigen. Ultrastructurally, these inclusions are intracytoplasmic and represent deposits of dense fibrillogranular material surrounded by unit membrane with microvilli ( Fig. 14-9 ).

Lymphoplasmacyte rich meningioma is the least common, least well characterized, and most controversial meningioma subtype. Many examples previously reported in the literature are now recognized as reactive or inflammatory lesions, rather than meningiomas. Nevertheless, there are legitimate examples of meningiomas with prominent intratumoral lymphoplasmacytic infiltrates. The significance awaits further investigation ( Fig. 14-9 ).

Microcystic meningioma exhibits a distinctive architecture of spidery cell processes that form variously sized microcysts to the extent that, to the uninitiated, the tumor may not be recognized as a meningioma. Closer inspection will reveal typical bland nuclei. Microcystic meningioma often shows morphologic features that overlap with those of angiomatous meningioma (rich vasculature) and secretory meningioma (occasional pseudopsammoma bodies) ( Fig. 14-10 ). All three of these meningioma variants—angiomatous, secretory, and microcystic—frequently display “degenerative” nuclear atypia, and in some tumors the morphologic features are so overlapping that any of the three appellations might be applied. In the absence of high-grade features (such as elevated mitotic activity or brain invasion), all three are benign, WHO grade I, subtypes with no prognostic significance.

Chordoid meningioma is characterized by cords of meningothelial cells typically surrounded by a rich myxoid matrix ( Fig. 14-11 ).

Clear cell meningioma is characterized by prominent cytoplasmic clearing ( Fig. 14-11 ).

Papillary meningioma represents a distinct variant of meningioma. Recognition of this entity has clinical significance because these neoplasms exhibit locally aggressive growth and are associated with late metastases. These neoplasms are composed of meningothelial cells arranged in papillary structures with central fibrovascular cores (perivascular pseudorosettes) ( Fig. 14-11 ).

Rhabdoid meningioma is another meningioma subtype with potential for aggressive clinical behavior. Tumor cells exhibit characteristic rhabdoid morphology, often lacking other typical architectural and cytologic features of meningioma.

Atypical and anaplastic meningiomas comprise the higher grade categories of meningiomas. Atypical meningiomas (WHO grade II) exhibit at least three of the following five histologic features: foci of micronecrosis, prominent nucleoli, sheeting architecture, small cell formation, or hypercellularity ( Figs. 14-12 ). Anaplastic meningioma (WHO grade III) exhibits morphologic features resembling sarcoma, carcinoma, or melanoma. These are among the rarest meningioma variants.

Brain invasive meningiomas exhibit increased potential for early recurrence and are therefore classified as WHO grade II. In cases in which it is uncertain whether the invaded tissue is brain parenchyma or reactive leptomeningeal tissue, immunostaining for GFAP or S-100 protein can be performed ( Fig. 14-13 ).

Grading of meningiomas is based on levels of mitotic activity ( Table 14-2 ). Upgrading of any meningioma histologic subtype is warranted when increased mitotic activity is present. Specifically, meningiomas with four or more mitoses per 10 contiguous high-power fields are classified as WHO grade II, and meningiomas with 20 or more mitoses per 10 contiguous high-power fields are classified as WHO grade III ( Fig. 14-13 ).

Meningiomas that invade osseous structures can provoke prominent reactive bone formation. Sometimes reactive new bone forms parallel striations. This orientation is best seen on specimen radiographs but can also be demonstrated during low power microscopic examination. Reactive bone formation may also take the form of haphazardly arranged bone trabeculae. Occasionally, the bone formation is so abundant that it overshadows underlying tumor cells.

Immunohistochemically, meningiomas are positive for epithelial membrane antigen. In the setting of cranial lesions, this feature is very helpful in distinguishing meningiomas from schwannomas and tumors of glial cell origin. As in all cells of mesenchymal origin, vimentin is strongly positive in meningiothelial cells. Approximately 20% of meningiomas show at least focal positivity for S-100 protein. Keratin is typically not present in meningioma, but it can be focally positive, especially in secretory meningioma.

Clinical Behavior

The vast majority of meningiomas are clinically benign and their eradication depends on the size of the lesion, specific topographic involvement, as well as involvement of the vital structures of the central nervous system. A small proportion of meningiomas exhibit locally aggressive behavior. These tumors rarely may exhibit metastatic potential with involvement of extracranial osseous sites. Both grading of meningiomas and their molecular characteristics correlate to some degree with clinical behaviors. In general, grade I meningiomas behave as benign tumors, and grade II are locally aggressive, whereas grade III meningiomas have some degree of metastatic potential. Meningiomas characterized by mutations of the TRAF7, KLF4, and SMO genes are distinct and nearly always show a benign clinical course with chromosomal stability and have a tendency to originate in the medial skull base. Meningiomas containing the mutant NF2 gene frequently exhibit loss of chromosome 22, are genomically unstable, and are more likely atypical. These tumors have a tendency to originate over the cerebral and cerebellar convexities.

Radiologic Features

The radiologic features of solitary fibrous tumor of the central nervous system typically mimic those of meningioma; that is, they are dura-based circumscribed masses that show enhancement after contrast administration ( Fig. 14-14 ). At the more aggressive end of the spectrum, hemangiopericytoma (cellular solitary fibrous tumor) has a tendency for early recurrence and metastasis, including a high propensity for extracranial skeletal metastases.

Gross Findings

Grossly the lesions are usually well delineated, firm, and nodular, with an overall fibrous appearance. On cut section, the nodular nature of the lesion is evident and the great white fibrous mass may have foci of myxoid change or hemorrhage.

Microscopic Findings

Solitary fibrous tumors are composed of spindle cells arranged in short ill-defined fascicles, described as a patternless pattern. A characteristic feature is the presence of striking hyalinization. The vasculature varies from narrow vascular channels to prominent open branching vessels referred to as hemangiopericytoma-like vasculature . The cellular variants of solitary fibrous tumors have overlapping features with soft tissue hemangiopericytoma. The solitary fibrous tumor family comprises a spectrum of tumors ranging from relatively indolent solitary fibrous tumor at one end to aggressive hemangiopericytoma (cellular solitary fibrous tumor) at the other ( Fig. 14-14 ). The microscopic features of solitary fibrous tumor in the central nervous system overlap with those of the more common ones that affect the soft tissue, predominantly the pleura. At the two ends of the spectrum, the tumors exhibit distinctive classical morphologic features, with solitary fibrous tumor displaying bland spindle cells separated by prominent bands of ropy collagen and strong diffuse immunoreactivity for CD34, whereas classical hemangiopericytoma is a highly vascular, densely cellular, mitotically active neoplasm in which CD34 reactivity is confined to the vasculature ( Fig. 14-13 ). However, it was recognized early on that many hemangiopericytomas display at least focal CD34 reactivity, and in fact the spectrum of solitary fibrous tumor embraces a wide range of transitional forms that blend in various proportions the morphologic, immunophenotypic and proliferative features of classical hemangiopericytoma and solitary fibrous tumor. Recognition of the kinship between solitary fibrous tumor and hemangiopericytoma was finally conclusively demonstrated beyond doubt by discovery of a shared underlying genetic signature.

Solitary fibrous tumors are characterized by the presence of a NAB2-STAT6 gene fusion in the vast majority of both soft tissue and central nervous system tumors ( Fig. 14-15 ). The fusion is caused by an inversion within chromosome 12 resulting in the juxtaposition of NAB2 and STAT6 neighbor genes. The breakpoint within STAT6 is conserved, and typically the fusion variants contain almost the entire STAT6 reading frame. There are shifting breakpoints within the NAB2 gene, but all of the variants retain the early growth response protein 1 binding domain (EBD). The transcriptional activation domain (TAD) of the STAT6 fusion partner is most likely responsible for the proliferation inducing activity of the chimeric NAB2-STAT6 protein. The nuclear localization of STAT6 protein driven by the NAB2 promoter in solitary fibrous tumors can be used as an auxiliary test in their differential diagnosis.

Definition

Schwannoma (neurilemmoma) is a benign peripheral nerve sheath tumor composed of Schwann cells that are frequently arranged in hypercellular and hypocellular areas, referred to as Antoni A and B tissue, respectively . Schwannomas are encapsulated and typically arise from a recognizable nerve trunk.

Incidence and Location

Intraosseous schwannomas arise most frequently in the mandible and sacrum. They have also been reported in a number of other locations, including the vertebral bodies, ulna, humerus, femur, tibia, patella, scapula, rib, maxilla, and small bones of the hands. Intraosseous schwannomas were also described in a setting of neurofibromatosis type 3 (schawannomatosis).

Clinical Symptoms

The most common symptoms are pain and localized swelling over the affected area.

Radiographic Imaging

Radiographically, the lesions are lytic, but a narrow sclerotic zone may be present at the periphery ( Fig. 14-18 ). The bone contour may be expanded with no periosteal reaction. The cortex may be thinned, but no true cortical destruction or extension into soft tissue is present. Although the lesions are primarily lytic, they may have incomplete internal trabeculation or lobulation ( Fig. 14-18 ). The radiographic appearance is usually interpreted as benign, but a specific diagnosis cannot be made from radiographic findings alone. It is difficult to differentiate intraosseous schwannoma on radiographs from other conditions that have similar radiographic features, such as solitary bone cyst, chondroblastoma, chondromyxoid fibroma, and giant cell tumor. CT scans show sharp delineation of the tumor and may disclose the dumbbell nature of the lesion ( Figs. 14-19 and 14-20 ). On MRI, schwannomas appear as uniformly contrast enhancing well-delineated lesions with an anatomic relationship to the adjacent nerve structures ( Figs.14-19 and 14-20 ).