Non-glial Tumors

Pathologic Features

Grossly, tumors are well demarcated and generally compress the adjacent parenchyma ( Fig. 10.1A ). Occasional tumors grow in a flat, en plaque pattern. A subset of atypical and anaplastic meningiomas may invade neural parenchyma. Hyperostosis of the overlying skull secondary to bone invasion may be encountered. Tumors may infiltrate skin and extracranial structures.

The majority of meningiomas are of the meningothelial, fibrous, or transitional types and are World Health Organization (WHO) grade 1 tumors ( Table 10.1 ). Specific histologic subtypes that have been associated with more aggressive behavior include chordoid and clear cell tumors (WHO grade 2) ( Fig. 10.2A–B ) and papillary and rhabdoid tumors (WHO grade 3) ( Fig. 10.3A–B ). Histologic grading of tumors into the atypical (WHO grade 2) and anaplastic (malignant) (WHO grade 3) categories is based on mitotic activity, degree of cellularity, small cell change, prominent nucleolation, sheet-like growth pattern, necrosis, brain invasion, and lack of differentiation (see Figs. 10.2C–E and 10.3C ). Brain invasive tumors are considered WHO grade 2 lesions (see Fig. 10.2E ). Preoperative embolization to reduce intraoperative bleeding may result in tumor necrosis (see Fig. 10.2F ); necrosis in this setting should not be used to grade the tumor. Rarely, high-grade tumors can metastasize outside the CNS (see Fig. 10.3D ).

By immunohistochemistry, approximately 80% of meningiomas stain with epithelial membrane antigen (EMA), vimentin and somatostatin receptor 2a (SSTR2a) immunoexpression. Approximately 20% to 40% of tumors are immunoreactive to S-100 protein. Focal positivity with antibodies to carcinoembryonic antigen (CEA) and cytokeratins may be observed. Ki-67 labeling indices generally correlate with tumor grade. Ultrastructural examination of the tumor is marked by the presence of prominent numbers of intermediate filaments, interdigitating cell processes, and desmosomal intercellular junctions.

Differential Diagnosis

Differential diagnostic considerations are numerous, given the phenotypic variability of these tumors. The fibrous variant of meningioma can be particularly problematic because of its bland spindled cell composition. Distinction of this lesion from schwannoma, especially in the cerebellopontine angle region, may be difficult. Schwannomas demonstrate diffuse S-100 protein immunoreactivity, Verocay body formation, biphasic Antoni A and Antoni B patterns, and a lack of psammoma body formation. Low-grade solitary fibrous tumors/hemangiopericytomas are generally CD34- and STAT 6-positive and marked by collagen material deposited between individual cells ( Fig. 10.4A–B ); they are negative for progesterone receptor and SSTR2a. Meningioangiomatosis is a rare neurofibromatosis type 2 associated lesion characterized by perivascular collars of meningothelial cells extending into the parenchyma ( Fig. 10.5 ), but it lacks the other worrisome histologic features that mark most brain invasive meningiomas. The other group of meningiomas that tend to be problematic with regard to the differential diagnosis includes the anaplastic tumors. According to WHO criteria, these tumors have areas that resemble carcinoma, melanoma, or sarcoma. Distinction of high-grade meningiomas from these various lesions may be challenging. In general, carcinomas demonstrate more widespread cytokeratin immunoreactivity. Melanomas are positive for S-100, HMB-45, and melan A. Differentiation of nondescript high-grade sarcomas from spindled, high-grade meningiomas may be difficult and requires ultrastructural evaluation in certain cases. Occasionally, high-grade astrocytomas may also have a spindled cell or sarcomatous appearance (gliosarcomas). Most gliomas demonstrate some degree of GFAP immunoreactivity. Hemangioblastomas and clear cell carcinomas show clear cytoplasmic features which may resemble clear cell meningioma. Inhibin (for hemangioblastoma) and PAX 8 positivity (for renal cell carcinomas) will respectively stain each of these lesions and help differentiate them from clear cell meningioma.

Pathologic Features

Benign lesions tend to be well circumscribed in contrast to sarcomas, which are often infiltrative. Sarcomas may have a fleshy appearance on sectioning and are frequently marked by areas of necrosis and hemorrhage.

Microscopically, a myriad of tumor types fall into this general category. The most commonly encountered sarcoma type in childhood is rhabdomyosarcoma. In adults, high grade solitary fibrous tumors are the most frequently encountered sarcoma type ( Fig. 10.6A–B ); these latter tumors are marked by randomly oriented cells with scant cytoplasm and a prominent staghorn vascular pattern. By immunohistochemistry, solitary fibrous tumors are generally STAT6- and CD34-positive and negative for EMA and S-100 protein (see Fig. 10.6C ). Grading is based on phenotype and mitotic counts. Criteria for subtyping sarcomas in the CNS should follow the rules for subtyping sarcoma elsewhere in the body ( Fig. 10.7A–B ). Many of these tumors represent metastasis from extra-CNS sites.

Differential Diagnosis

Differential diagnostic considerations for higher-grade tumors include metastatic spindled carcinomas, melanomas, other sarcoma types, anaplastic meningiomas, and gliosarcoma. In contrast to the majority of sarcomas, metastatic carcinomas demonstrate some degree of cytokeratin immunoreactivity, whereas melanomas demonstrate S-100, melan A, SOX 10, and HMB-45 immunoreactivity. STAT6 may be helpful in distinguishing solitary fibrous tumor/hemangiopericytoma from other nondescript high-grade sarcomas or anaplastic meningiomas if no differentiating features are evident. Lower grade lesions may resemble fibrous meningiomas or schwannomas; again, immunohistochemistry may be helpful in sorting out these differentials. Gliosarcomas contain a glioblastoma component that is GFAP immunoreactive.

Differential Diagnosis

From a clinical and radiographic standpoint, pilocytic astrocytomas can resemble hemangioblastomas; however, the tumors look very different histologically. Occasionally, a biopsy sample taken at the edge of a hemangioblastoma with numerous Rosenthal fibers and piloid gliosis may be confused with pilocytic astrocytoma. Metastatic clear cell carcinoma of renal origin can also resemble hemangioblastoma. This resemblance is particularly problematic in the setting of Von Hippel-Lindau disease, where both lesions are more likely to appear. In general, renal cell carcinomas are EMA-, PAX8-, PAX2- and CD10-positive, may demonstrate areas of necrosis and mitotic activity, and do not stain with inhibin A.

Pathologic Features

Grossly, melanocytosis is characterized by black pigmentation of the leptomeninges. Melanocytomas and melanomas are relatively circumscribed lesions with variable degrees of pigmentation. Melanoma may also be marked by variable amounts of hemorrhage and necrosis.

Histologically, melanocytosis is characterized by a diffuse proliferation of nevoid cells in the leptomeninges ( Fig. 10.9A ). Focally, extension into the Virchow-Robin spaces may be present. Melanocytomas are marked by a proliferation of monomorphic-appearing cells that may be polygonal or spindled in configuration with round vesicular nuclei, prominent nucleoli, and a variable degree of cytoplasmic melanin (see Fig. 10.9B ). Melanomas, in contrast to melanocytomas, are generally more pleomorphic, have increased mitotic activity and an infiltrative growth pattern, and more frequently demonstrate evidence of necrosis (see Fig. 10.9C ). Ultrastructurally, all lesions are marked by the presence of melanosomes and a lack of junctions. By immunohistochemistry, all lesions are positive for S-100 protein, melan A (MART-1), SOX 10, and HMB978-0-323-71344-3.

Differential Diagnosis

Differentiating melanin-poor melanocytomas and melanomas from other tumors may at times be difficult. The immunohistochemical profile is somewhat distinctive and can be helpful in excluding most other tumor types. A variety of other primary CNS neoplasms, including gliomas, medulloblastomas, and schwannomas, may focally contain melanin pigmentation.

Pathologic Features

Grossly, chordomas are infiltrative, lobulated masses with a mucoid appearance on sectioning. Focal areas of cartilaginous differentiation (chondroid chordoma) may be observed ( Fig. 10.10A ).

Histologically, tumors are marked by a lobulated architectural pattern with fibrovascular septa. Epithelioid cells are arranged in cords or rows (see Fig. 10.10B ). Many of the cells may have a prominently vacuolated cytoplasm (physaliphorous cells) (see Fig. 10.10C ), and occasional mitotic figures and mild nuclear pleomorphism may be present. Ultrastructurally, the tumors are characterized by abundant cytoplasmic mucus vacuoles and desmosomal junctions. Tumors stain positively with antibodies to vimentin, cytokeratin, EMA, brachyury, and S-100 protein. Rare anaplastic tumors (particularly in children) may demonstrate INI-1 loss.

Differential Diagnosis

Metastatic mucinous adenocarcinoma may resemble chordoma but generally does not stain with S-100 protein. Chordoid meningiomas may superficially resemble chordoma, although they typically arise in other locations and do not usually demonstrate prominent cytokeratin positivity. In tumors with a chondroid component, differentiation from chondrosarcoma may be an issue. In general, the cartilaginous component in chondrosarcoma appears malignant with large pleomorphic nuclei (see Fig. 10.10D ). Chondrosarcomas are cytokeratin- and EMA-negative.

Pathologic Features

Grossly, papillomas are somewhat circumscribed papillary masses. In contrast, choroid plexus carcinomas are solid masses frequently punctuated with necrosis and an infiltrative margin.

Histologically, choroid plexus papillomas are characterized by a proliferation of bland choroid plexus epithelial cells lining fibrovascular cores ( Fig. 10.11A ). Minimal mitotic activity and cytologic atypia are present. Atypical papillomas (WHO grade II) are marked by two or more mitoses per 10 high-power fields (see Fig. 10.11B ). In contrast, carcinomas are marked by nuclear atypia, increased mitotic activity, increased cellularity, necrosis, loss of papillary pattern, and brain invasion (see Fig. 10.11C ). Ultrastructurally, choroid plexus tumor cells are characterized by microvilli, tight junctions, and interdigitating membranes. By immunohistochemistry, tumors generally stain with antibodies to keratin and S-100 protein. Focal GFAP immunoreactivity and immunostaining with transthyretin may also be observed.

Differential Diagnosis

Particularly in children, differentiation of papillary ependymoma from choroid plexus papilloma may at times be problematic. In general, papillary ependymomas have a gliovascular core, demonstrate more widespread GFAP immunoreactivity, and are marked by the formation of perivascular pseudorosettes and true ependymal rosettes. Metastatic papillary carcinomas are in the differential diagnosis of choroid plexus carcinomas. Distinction of these two tumor types may be quite difficult on occasion. Most metastatic carcinomas occur in older patients and are less likely to be positive for transthyretin, S-100 protein, and GFAP.