—  SPECIALTY CONFERENCE  —

Neuropathology

Case 4 - Clear Cell Meningioma, Spinal Drop Metastasis vs. Second Primary

Daniel J. Brat
Emory University School of Medicine
Atlanta, GA


Click on each slide thumbnail image for an enlarged view
Clinical History
A 32-year-old female developed headaches and blurred vision over the course of three months. Magnetic resonance imaging (MRI) revealed a large, contrast-enhancing suprasellar mass with multiple cystic components. The tumor impinged on the optic chiasm superiorly and extended posteriorly and inferiorly into the posterior fossa, where it compressed the right side of the pons. The neoplasm was surgically resected. Follow-up MRI after 12 months showed no residual tumor.


Case 4 - Figure 1 - Pre- and post-contrast sagittal MR images of the spine showing an intradural mass extending from the T12 to the S1 level. The tumor distends the thecal sac and obliterates the view of the spinal cord.
Case 4 - Figure 2 - Pre- and post-contrast axial MR images of the spine demonstrating a solid, homogeneous mass greatly expanding the thecal sac within the vertebral canal and extending into soft tissues posteriorly.
Case 4 - Figure 3 - Low magnification H&E-stained section of clear cell meningioma showing a homogeneous tumor of moderate cellularity with a clear cell population and abundant intracellular hyaline stroma.


Case 4 - Figure 4 - High magnification H&E-stained section of clear cell meningioma showing tumor cells with clear, glycogen-rich cytoplasm and round, bland nuclei. Intracellular hyaline stroma is deposited in spherical configurations and shows multifocal, punctate crystalline deposits.
Case 4 - Figure 5 - H&E-stained cytologic smear preparation of clear cell meningioma demonstrating classic meningothelial cytologic features including whorls, delicate nuclear chromatin, and wispy cytoplasm.
Three years after the operation, the patient developed progressively worsening back and leg pain, lower extremity weakness, as well as bowel and bladder dysfunction. She required a wheelchair and could not walk without assistance. MRI of the spinal cord showed a contrast-enhancing intradural mass that filled and expanded the thecal sac, extending from the T12 to the S1 level. At surgery, the tumor was found to entrap spinal cord and spinal roots. It also eroded through the dura in multiple locations. The tumor was resected piece by piece from the surrounding normal structures. The specimen from the spinal resection was sent for pathological examination.

Diagnosis
Clear cell meningioma, spinal drop metastasis vs. second primary.

Discussion
Clear cell meningioma is one of 13 histologic subtypes of meningioma recognized by the most recent WHO classification [1]. It is rare, accounting for 0.2% of all meningiomas in a series from the Mayo Clinic [2]. The higher frequency of conventional meningiomas in females is not apparent for clear cell subtypes, although the number of cases in the literature remains small. Patient age at presentation is younger for clear cell meningioma (mean, 29 years in one series) and numerous examples of pediatric clear cell meningiomas have been reported, both in the setting of NF2 and sporadically [2, 3, 4, 5, 6] .

Clear cell meningiomas are defined by their histologic appearance, which is both unique and consistent. They have moderate cellularity with a sheet-like or lobulated growth pattern [1, 2] . Their defining cell type is clear due to heavy glycogen content and is present either singly or in small groups, with intercellular borders easily seen. Nuclei are round and bland, with inconspicuous nucleoli, and lack any appreciable mitotic activity. Separating tumor cell clusters is a distinctive hyalinized stroma that often is disposed in spherical configurations with central, punctate crystalline deposits. The appearance of the stroma, together with intervening clear, bland tumor cells, forms a histologic picture that is memorable, yet not classically meningothelial. Only occasionally will tumor cells show a tendency toward whorl formation and psammoma bodies are not typical. Classic cytologic features of meningiomas, including whorls, wispy cytoplasm, and dispersed, delicate chromatin within ovoid nuclei, are much better appreciated on smear preparations.

Since clear cell meningiomas do not always have characteristic meningothelial features, additional studies can be supportive in reaching the diagnosis. First, due to the heavy content of cytoplasmic glycogen, tumor cells stain intensely with PAS stains and are labile to diastase treatment [2, 7] . Like other meningiomas, nearly all clear cell tumors show a membranous pattern of immunoreactivity for EMA and are strongly reactive for vimentin. Nuclear progesterone receptor (PR) staining is seen in 77% of tumors, but estrogen receptor staining is usually absent [2]. Stains for CAM 5.2 and S-100 protein are negative. Ultrastructural features can be used if necessary in order to define these tumors as meningothelial: cytoplasmic intermediate filaments, some taking the form of whorls; interdigitating cell membranes; and intercellular junctions, mostly desmosomes are nearly always present [2, 8] .

Given the high degree of tumor hyalinization, the modest cellularity, the bland cytologic features, and the lack of mitotic activity, it may be surprising that clear cell meningiomas are biologically aggressive compared to conventional grade I meningiomas. 61% of clear cell meningiomas recurred in the series by Zorludemir et al. and other examples of aggressive behavior have been well documented [2, 7, 9, 10] Indeed, the WHO has recognized this tendency by designating clear cell meningiomas as WHO grade II based on their histologic appearance alone [1]. The other grade II histologic subtype is the chordoid meningioma, while grade III histologic subtypes include papillary and rhabdoid meningioma. Reasons for aggressive clinical behavior are not apparent.

From the series of 13 clear cell meningiomas in the Mayo Clinic study and the additional cases in the literature, it is evident that the anatomic distribution is distinct [2, 3, 4, 5, 6, 7, 8, 9, 10, 11] . Clear cell meningiomas occur frequently in the spinal canal, especially at the lumbar level, and posterior fossa, and less commonly in the supratentorial compartment [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12] . Other unusual locations are within the spinal cord parenchyma and within the 4th ventricle [3, 4, 11] . Growth in the cauda equina has been documented in a number of cases [6, 12] . Multifocal tumors at initial clinical presentation have been reported, seemingly with a frequency greater than classic meningiomas [2, 5] . One possibility is that the unusual locations of clear cell meningiomas preclude their total surgical resection, making their tendency to recur more likely. Another possibility is that these tumors are more frequently multifocal and "recur" at other locations due to the emergence of a second primary. In the case presented, it is not entirely clear if the second tumor in the spinal canal represented a drop metastasis from the suprasellar mass or arose as a second primary.

Other than location, the neuroimaging features of clear cell meningioma are not distinguishing: they are most often extra-axial, iso-intense to CNS on T1- and T2- weighted MRI, and demonstrate fairly homogeneous contrast-enhancement [6, 9, 12] . The histologic appearance is sufficient for establishing the diagnosis of clear cell meningioma once the pathologist is familiar with its features. Among the entities most confused with clear cell meningioma are other meningiomas subtypes that contain clear cytoplasm. Chief among these is microcystic meningioma, which is composed of cells with clear cytoplasm, but also has numerous small cystic spaces between cells that are filled with pale, mucinous fluid. Microcystic meningiomas lack the characteristic hyaline stroma that is abundant in clear cell meningiomas and do not have glycogen rich, PAS-positive cytoplasm.

References

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