Intra-Axial Neoplasms

CHAPTER 32 Intra-Axial Neoplasms



Primary neoplasms of the central nervous system (CNS) are relatively infrequent, accounting for 16.5 to 18 cases per 100,000 person-years. However, they are a significant health concern.


Primary CNS neoplasms are histologically diverse and may arise from neuroepithelial tissue (e.g., astrocytic tumors, oligodendroglial tumors, ependymal tumors, embryonal tumors) or the hematopoietic system (primary CNS lymphoma). Neuroepithelial tissue consists of glial cells, neuronal cells, neuroblastic cells, pineal parenchymal cells, and residual embryonal cells. Most intra-axial neoplasms are of glial origin, accounting for 40% to 50% of primary CNS neoplasms.1 The glial neoplasms arise from astrocytes, oligodendrocytes, ependymal cells, or their derivatives in the choroid plexus. The ganglion cell tumors (ganglioglioma, gangliocytoma) are composed of abnormal neoplastic neuronal cells or of a combination of neuronal and astrocytic elements.


Primary CNS neoplasms are graded according to the World Health Organization (WHO) classification system. The high-grade glial neoplasms are differentiated from the low grade on pathology by the presence of increased cellularity, increased mitotic activity, necrosis, and vascular proliferation. In a surgical series of stereotactic brain biopsies—consisting of 5000 specimens—the most common intra-axial brain masses were high-grade primary neoplasms (36%), low-grade primary neoplasms (33%), metastasis (8%), lymphoma (5%), demyelinating inflammatory lesions (3%), infarcts (2%), and abscesses (1%).2,3


Imaging plays an integral role in the detection, diagnosis, and management of these lesions, and advanced imaging, such as perfusion and MR spectroscopy, may help narrow the differential diagnosis and assist in post-treatment follow-up. However, the limitations of conventional MRI and advanced imaging must be kept in mind when interpreting the results. Conventional MRI is currently limited in its ability to demarcate the exact margins of infiltrative tumors, to accurately grade the neoplasm, and to monitor early changes after treatment. An example of the limitation of advanced imaging is in the evaluation of MR spectroscopy where there are no unequivocal cutoff metabolite peaks that clearly differentiate a neoplastic lesion from a non-neoplastic one, and low-grade neoplasms may have spectra that are similar to high-grade neoplasms, lymphoma, and metastases (i.e., elevation in choline [Cho], reduction in N-acetyl aspartate [NAA], and presence of a lipid/lactate peak). Tumefactive demyelinating lesions may show this pattern as well. However, in a review by Al-Okaili and associates, it was found that a Cho/NAA cutoff ratio of 2.2 could reliably separate high-grade neoplasms from low-grade neoplasms and non-neoplastic lesions.3


Perfusion-weighted imaging may be of benefit in assessing angiogenesis induced by neoplasms. The vessels formed in a neoplastic process tend to be abnormal and leaky, thus resulting in increased permeability parameters on perfusion MRI. Several studies have demonstrated a correlation of tumor blood volume with the grade of neoplasm.46 Law and colleagues observed that a relative cerebral blood volume (rCBV) threshold value of 1.75 provided a sensitivity of 95% and positive predictive values of 87% for distinguishing between high- and low-grade gliomas.4 Because metastases tend to induce angiogenesis as well, the perfusion parameters of metastatic lesions tend to overlap with high-grade neoplasms.


Recent research has demonstrated that diffusion tensor imaging (DTI) has important potential benefits in surgical planning owing to the ability to detect white matter tracts in the region of the neoplasm.7,8 The ability to assess whether the neoplasm has shifted the tracts versus infiltrating them is important information for the neurosurgeon and can assist in determining the method of approach and the extent of resection that is possible.



PILOCYTIC ASTROCYTOMA


Pilocytic astrocytoma is a slowly growing, well-circumscribed neoplasm classified by the WHO as a grade I glioma.


In the past, pilocytic astrocytomas were also referred to as “spongioblastoma polare” owing to their histiologic resemblance to the spongioblastic cells of the fetus. This term is no longer in use. Pilocytic astrocytoma is also called “juvenile” pilocytic astrocytoma—a prefix no longer required. In addition, some refer to pilocytic astrocytomas by their location (i.e., optic nerve glioma, hypothalamic glioma).



Epidemiology


Pilocytic astrocytomas are the most common form of glioma in childhood and most frequently develop in the first two decades of life; 80% occur in patients younger than 20 years old.9 Rarely, they arise in patients older than 50. They comprise 5% to 10% of all gliomas, and there is no strong gender predilection. However, some series have reported a slightly higher incidence in females (11 : 9). Pilocytic astrocytoma may arise anywhere within the neuraxis, but within the pediatric population (<15 yr) they arise more frequently infratentorially and comprise 85% of all cerebellar neoplasms in the pediatric age group.9 Other common sites are the optic nerve, optic chiasm and hypothalamus, basal ganglia, and thalamus.


Pilocytic astrocytomas are associated with neurofibromatosis type 1 (NF-1), occurring in 15% to 21% of patients with this disease.9 In these patients the intraconal optic nerve and chiasm are most commonly involved (Fig. 32-1). The majority of optic pathway gliomas occur before 6 years of age, and there is a female predominance (2 : 1).



Pilocytic astrocytomas have benign biologic behavior with a survival rate of up to 94% at 10 years.9 Disseminated disease and recurrence are very rare. Interestingly, when metastatic disease occurs, it can do so without increased mortality, unlike metastases from higher-grade neoplasms (Fig. 32-2).






Pathology


On gross pathology, pilocytic astrocytomas are soft, wellcircumscribed lesions. Fluid accumulation (“cyst formation”) is commonly seen (Fig. 32-3). In older lesions, hemosiderin or calcium may be seen. Calcification tends to occur more often in tumors arising from the optic nerve or hypothalamic-thalamic regions. Lesions involving the optic nerve result in elongation and fusiform widening of the nerve.



Pilocytic astrocytomas have increased capillary vascularity and low to moderate cellularity. In long-standing neoplasms the vessels may become hyalinized and glomeruloid. A biphasic pattern of two astrocyte populations having varying proportions of compact bipolar cells with Rosenthal fibers (nonfilamentous electron-dense masses) and loose-textured multipolar cells with microcysts and eosinophilic granular bodies/hyaline droplets is seen (Figs. 32-4 and 32-5). The presence of eosinophilic granular bodies is thought to indicate slow growth and low histologic grade and is associated with an improved prognosis. Neoplastic changes involving the cyst wall have been reported.12 Infiltration into the surrounding tissues may be seen but is usually shallow, especially in comparison with the adult or diffuse astrocytomas. This occurs more frequently in tumors involving the optic nerve and chiasm, and, commonly, there is poor demarcation between tumor and normal tissue. Pilocytic astrocytomas involving the cerebellum may infiltrate the leptomeninges, resulting in fixation of the cerebellar folia and filling of the sulci (Fig. 32-6).





On immunohistochemical evaluation, pilocytic astrocytomas are usually strongly and nearly diffusely positive for glial fibrillary acidic protein (GFAP), which is an intermediate filament found in the cytoplasm of astrocytes. S-100 protein, which is found in all cells derived from the neural crest, is also positive. MIB-1 (a nuclear marker of proliferation) rates are usually low.



Imaging


Pilocytic astrocytomas are well-circumscribed lesions that enhance on postcontrast imaging. Fluid formation is common, and the classic description is that of a “cyst and nodule” (Fig. 32-7). Occasionally, calcification (up to 25%) may be seen and hemorrhage has been reported (Figs. 32-8 and 32-9). Pilocytic astrocytomas occasionally may enhance in a ring-like pattern, suggesting the morphology of a higher-grade neoplasm. In these cases, location (cerebellum) and age (<15 years) may suggest benign fluid, rather than necrosis, as the cause of the ring enhancement.





Four imaging patterns of pilocytic astrocytomas have been described: (1) enhancing mural nodule and nonenhancing cyst, (2) enhancing cyst wall and enhancing mural nodule, (3) “necrotic” mass with central nonenhancing region, and (4) predominantly solid mass with minimal or no cyst.12 Cyst wall enhancement does not necessarily imply there is tumor involvement, and removal of the cyst wall is not related to improved survival.13,14 Some pilocytic astrocytomas may show thin rim enhancement from reactive gliosis surrounding the fluid.


CSF dissemination is rare (2%-12%) and increases in the setting of tumors located in the hypothalamus, in cases of partial resection, and in patients younger than 4 years old at the time of diagnosis. Dissemination tends to occur within the first 3 years after diagnosis.15




MRI


On MRI, the solid portion of the neoplasm is typically isointense to hypointense on T1-weighted (T1W) imaging and hyperintense on T2-weighted (T2W) imaging to gray matter. The cystic portion is often hyperintense to CSF from protein (Fig. 32-10). The cyst contents do not suppress on FLAIR. The solid portion enhances on postcontrast imaging. Occasionally, the wall around the fluid may demonstrate rim enhancement. Rarely, leptomeningeal metastases may be seen.



In these low-grade tumors, MR spectroscopy demonstrates elevation in choline and a reduction in NAA, a pattern that is also seen in higher-grade neoplasms. There is minimal elevation in the lipid peak, and lactate peaks are elevated (Fig. 32-11). The elevation in lactate may represent alterations in mitochondrial metabolism or represent variability in glucose utilization rates among low-grade astrocytomas and not necrosis because necrosis is rare in pilocytic astrocytomas.16





PILOMYXOID ASTROCYTOMA


Pilomyxoid astrocytoma is a WHO grade II neoplasm that is closely related to pilocytic astrocytoma.


In the past, pilomyxoid astrocytomas were referred to as infantile pilocytic astrocytomas. The term pilomyxoid was introduced in 1999.








PLEOMORPHIC XANTHOASTROCYTOMA


Pleomorphic xanthoastrocytoma (PXA) is a WHO grade II neoplasm. Occasional examples have anaplastic features. Before immunostaining, PXAs were thought to be mesenchymal neoplasms of the meninges and brain.






Pathology


PXAs are peripherally located neoplasms and involve the leptomeninges (Fig. 32-15). Cyst formation is common, and a “cyst and nodule” appearance is common.



Pleomorphic xanthoastrocytomas have a variable histologic appearance, hence the name “pleomorphic.” Mononucleated or multinucleated giant astrocytes with variable nuclear size and staining are seen. They have a dense reticulin network and lipid (xanthomatous) deposits within the tumor cells. The term xanthoastrocytoma refers to large cells with intracellular lipid accumulation (Fig. 32-16). Despite a circumscribed appearance, most PXAs demonstrate extension into the surrounding brain. Even though the tumor is frequently attached to the leptomeninges, dural invasion is uncommon. Necrosis within the tumor portends a poorer prognosis.25 Mitoses are usually absent or rare; however, atypical PXAs demonstrate high mitotic activity and marked hypercellularity and necrosis. These may be considered grade III or anaplastic PXA.



Immunohistochemical analysis demonstrates the presence of glial fibrillary acidic protein (GFAP) and S-100 (present in cells derived from the neural crest); and neuronal markers such as synaptophysin (protein present in neurons in the brain and spinal cord that participate in synaptic transmission), class III β-tubulin (a neuronal marker), and NF proteins (play an important role in neuronal development) are also described. TP53 is the tumor suppressor gene, and mutations occur in many human cancers. Analysis for the TP53 mutation is negative or only focally positive. In one study of PXAs that demonstrated malignant progression, histochemical analysis revealed GFAP positivity in 100% and S-100 and TP53 were expressed in 67% but synaptophysin and NF protein were absent.26 The MIB-1 index for PXAs is typically less than 1%.



Imaging


The classic imaging appearance of PXAs is that of a peripherally located “cystic” supratentorial mass. However, 52% do not have macroscopic fluid changes.1 Lesions may be well circumscribed or poorly defined.






DIFFUSE ASTROCYTOMA


Diffuse astrocytomas are diffusely infiltrating primary brain neoplasms of astrocytic origin that are classified as WHO grade II. Diffuse astrocytomas are also referred to as low-grade diffuse astrocytomas and as grade II astrocytomas but most often simply as “astrocytoma.”







Imaging




MRI


Diffuse astrocytomas are low in signal on T1W imaging and may expand the white matter and adjacent cortex. They may cause loss of signal contrast between gray and white matter. On T2W imaging they are hypointense to hyperintense and may appear circumscribed. This is deceptive, because pathologically they are not discrete. Surrounding or spreading vasogenic edema is uncommon, and calcification, cysts, and hemorrhage are rare. They do not enhance on postcontrast imaging (Fig. 32-20).



MR spectroscopy should show an elevation of choline and a reduction in NAA. A high myoinositol (mI)/creatine (Cr) ratio is also present (0.82 ± 0.25).30 On dynamic contrast-enhanced T2*W the rCBV is typically low and should be lower than values seen in the high-grade astrocytomas; rCBV is typically less than 1.75.4 A study by Danchaivijitr and coworkers found that evaluation of the rCBV was able to distinguish between patients whose tumor did not transform to a higher grade and those whose tumor did over a 23-month observation period. In the nontransforming stable neoplasms the rCBV measurements remained low, whereas in those tumors that transformed, the mean rCBV value at the point of transformation was elevated to 5.36 ± 3.01. The elevated rCBV occurred before the development of contrast enhancement and may be an “early warning signal.”29


An assessment of the utility of DTI in differentiating diffuse astrocytomas from anaplastic was performed by Goebell and associates, who found that the fiber tracts were better preserved along the periphery of low-grade (II) neoplasms, whereas the tracts tended to be disarranged (lower anisotropy) in high-grade gliomas. Within the center of both low- and high-grade gliomas the fractional anisotropy (FA) was low, which was consistent with a high degree of disorganization of myelinated fiber tracts.31



ANAPLASTIC ASTROCYTOMA


Anaplastic astrocytomas are WHO grade III, diffusely infiltrating neoplasms. They are also referred to as grade III astrocytomas. Confusing synonyms include “malignant astrocytoma,” “malignant glioma,” and high-grade astrocytoma. However, these terms have also been used for glioblastoma, which is a WHO grade IV lesion.







Imaging





GLIOBLASTOMA


Glioblastoma multiforme (GBM) is the most malignant of the neoplasms with a primary astrocytic differentiation. Because it was thought to arise from the most primitive precursor of the stromal cell population (the glioblasts) and its gross morphology is highly variable and complex, it was given the name “glioblastoma multiforme.”33 The name is somewhat of a misnomer because GBMs are currently thought to arise from progressive dedifferentiation of mature astrocytes and not from rests of immature glioblasts. Glioblastomas are also referred to as grade IV astrocytoma.




Jan 22, 2016 | Posted by in NEUROLOGICAL IMAGING | Comments Off on Intra-Axial Neoplasms
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