A Rare Case of Xanthomatous Meningioma.

Xanthomatous meningioma is an extremely rare subtype of metaplastic meningiomas with few cases reported in the literature. Histopathologically, it is composed of oval-shaped cells that have central nuclei and cytoplasm with lipid-filled vacuoles, resembling macrophages. Here, the authors present a case of xanthomatous meningioma and discuss the hypotheses related to its origin and the differential diagnosis. A 40-year-old woman presented with an increased headache complaint over the past month. A computed tomography scan revealed a heterogeneous mass on the right parietal lobe, following which a right craniotomy was done. Microscopic examination showed neoplastic meningothelial cells with whorl formation and areas of xanthomatous changes. Both meningothelial and xanthomatous cells were positive with vimentin, progesterone, and epithelial membrane antigen. CD68 and lysozyme were expressed only in the xanthomatous component, and there was no expression with periodic acid-Schiff (PAS) stain and PAS-diastase. As the diagnostic criteria of atypical meningioma were not observed, a diagnosis of xanthomatous meningioma, WHO grade I, was made. Owing to the characteristic xanthomatous changes, its differential diagnosis includes grade II clear cell meningioma, Rosai-Dorfman disease, and hemangioblastoma. To avoid misidentifying these cells as macrophages, a high degree of awareness of this unique subtype of meningioma is required. Copyright:

INTRODUCTION

Meningiomas are among the most common tumors of the central nervous system.[1] They originate from arachnoid cap cells and can present a variety of epithelial and mesenchymal-like characteristics.[2] Metaplastic meningioma is a variant of meningioma with focal or diffuse mesenchymal components including osseous, cartilaginous, lipomatous, myxoid, and xanthomatous tissue, according to the World Health Organization (WHO) Classification of Tumors of the Central Nervous System.[2] However, it is not a true metaplasia itself but rather contains cytoplasmic fat accumulation, vacuolization, or other changes in meningothelial cells.[1] Xanthomatous meningioma is an extremely rare subtype of metaplastic meningioma that is composed of oval-shaped cells that have central nuclei and cytoplasm with lipid-filled vacuoles. To the best of the authors’ knowledge, only 17 such cases have been reported in the literature,[345678910111213] and thus there is a paucity of knowledge regarding the same. This case report is presented with the aim of discussing the hypotheses related to origin of xanthomatous meningioma and the differential diagnosis of this extremely rare subtype.

CASE REPORT

A 40-year-old woman was admitted to our neurosurgical clinic due to increasing headache complaints over the past month. A computed tomography scan revealed a heterogeneous mass on the right parietal lobe [Figure 1a and b]. After obtaining informed consent, a right craniotomy was done with a preliminary diagnosis of space-occupying lesion, and an intraoperative consultation was performed. The frozen material was in the volume of 1 cc, and after the frozen procedure was completed, a diagnosis of meningeal tumor was made. The remaining gross material was described as 7 × 6× 6 cm, irregularly shaped with soft consistency, partially hemorrhagic appearance, and partly processed. On histopathological examination, neoplasm comprising monotonous cells with eosinophilic and transparent cytoplasm was observed under the light microscope. Whorl formation was observed occasionally. Mitotic count was 1–2 on 10 high-power fields. Round cells with foamy cytoplasm were suggestive of xanthomatous changes [Figure 2]. In addition, cholesterol clefts were seen in some areas.

Figure 1

(a and b) Axial head computed tomography scan revealing heterogeneous mass starting from the right parietal region and extending toward the midline, brain parenchyma has been pushed, and the mass causes compression in the lateral ventricle

Figure 2

Meningothelial tumor cells with xanthomatous changes (H and E, ×100), inset: Cholesterol clefts with meningothelial and xanthomatous cells (H and E, ×100)

In immunohistochemical analysis, both meningothelial and xanthomatous cells were positive with vimentin and progesterone and showed mild positivity with epithelial membrane antigen (EMA). CD68 and lysozyme were expressed only in the xanthomatous component [Figure 3a-d], and there was no expression with periodic acid-Schiff (PAS) stain and PAS–diastase. In addition, the Ki-67 index was <5%. The diagnostic criteria of atypical meningioma were not observed, such as necrosis, brain invasion, macronucleoli, small cell formation, high nucleus/cytoplasm ratio, patternless, or sheet-like growth. Mitotic activity was very low. Based on these findings, a diagnosis of xanthomatous meningioma, WHO grade I, was made. The patient did not have any postoperative complications in the 4 years of follow-up at the time of reporting this case.

Figure 3

Immunohistochemical features: (a) Vimentin (×200) and (b) epithelial membrane antigen (×100) were expressed both meningothelial and xanthomatous components. (c) CD68 (×100) and (d) lysozyme (×400) were expressed in the xanthomatous component

DISCUSSION

Meningiomas are slow-growing neoplasms that are composed of meningothelial cells of the arachnoid layer.[2] They are classified into three-tiered grading according to the WHO: grades I, II, and III. Most meningiomas have benign histopathology and thus correspond to grade I. Grades II and III meningiomas are associated with worse clinical outcomes. Xanthomatous meningioma, which is a subtype of metaplastic meningioma, is classified as grade I. It was described by Kepes in 1994,[3] and to the best of the authors’ knowledge, only 17 cases have been recorded in the literature.[345678910111213] The clinicopathological comparison of these cases and the present case was made in Table 1. Although xanthomatous meningioma is considered as grade I, Taraszewska et al.[14] reported three atypical meningiomas and two anaplastic meningiomas with xanthomatous changes. In our case, the diagnostic criteria of atypical meningioma are absent and graded as WHO grade I meningioma. In another case, Ijiri et al.[5] reported xanthomatous meningioma in a 10-year-old child with a history of radiotherapy for ependymoma. There was no reported history of radiotherapy in any of the other cases in the literature, including our case.

Table 1

Clinicopathological comparison of xanthomatous meningioma cases

Case number	Age (Years)	Gender	Location	Immunohistochemistry findings	Reference number
1	24	Male	Right parietal	CD68 (+), vimentin (+)	[3]
2	2	Female	Posterior pyramid	EMA (+)	[4]
3	10	Male	Right frontal	CD68 (+), HAM56 (+), vimentin (+)	[5]
4	58	Female	Right frontal	EMA (+), Ki-67 (<5%)	[6]
5	27	Female	Right petrous bone	EMA (+), S100 (−), Ki-67 (<5%)	[6]
6	49	Female	Left parietal	EMA (+), S100 (−), Ki-67 (<5%)	[6]
7	59	Female	Right frontal	EMA (+), S100 (−), Ki-67 (<5%)	[6]
8	70	Female	Left sphenoid, small wing	EMA (+), S100 (−), Ki-67 (<5%)	[6]
9	79	Male	Left occipital	EMA (+), S100 (−), Ki-67 (<5%)	[6]
10	61	Female	Right occipital to parietal	EMA (+) CD68 (+) vimentin (+) lysozyme (+) Ki-67 (2.2%)	[7]
11	76	Male	Left parasagittal to frontal	EMA (+) CD68 (+) vimentin (+) lysozyme (+) adipophilin (+) Ki-67 (2.1%)	[8]
12	22	Male	Sinus region	EMA (+), vimentin (+), GFAP (−), Ki-67 (1%)	[9]
13	68	Male	Right frontal	EMA (+), vimentin (+), GFAP (±), Ki-67 (1%)	[9]
14	24	Female	Tempora-parieto-occipital region	EMA (+), Ki-67 (3.2%)	[10]
15	32	Male	Right frontal to parietal	EMA (+), CD68 (+) adipophilin (+) (xanthomatous area), Ki-67 (3%)	[11]
16	61	Male	Right parietal	EMA (+), vimentin (+), CD68 (+), GFAP (−), Ki-67 (1%)	[12]
17	83	Female	Left fronto-temporal region	EMA (+), PR (+), Vimentin (+), S-100 (+), CD68 (+), CD11c (+), p53 (weak+), CK (–), CD34 (–), Ki-67 (< 1%)	[13]
18.	40	Female	Right parietal	EMA (+), CD68 (+), vimentin (+), PR (+), lysozyme (+) Ki-67 (<5%)	Present case

EMA – Epithelial membrane antigen; PR – Progesterone; GFAP – Glial fibrillary acidic protein; PR – Progesterone receptor; CK – Cytokeratin

The most important finding that helps in diagnosis is xanthomatous cells. While its appearance is similar to blood-borne macrophages, xanthomatous cells were identified as meningothelial by ultrastructural characteristics of complex plasmalemmal interdigitations bound by desmosomes and hemidesmosome-like intercellular junctions on electron microscopic investigations.[35614]

Macrophages are not known to display complex plasmalemmal interdigitations or connect through desmosomes and hemidesmosomes to neighboring cells.[3] Immunohistochemical staining is also helpful in diagnosis. Xanthomatous cells are immunohistochemically positive with EMA and vimentin. This indicates that it is of meningothelial origin, also given its ultrastructural features.

In our case, CD68 and lysozyme, which are histiocytic markers, were also expressed. This expression was also seen in several cases in the literature and made it open to interpretation about the origin of xanthomatous cells.[3578111213] When resolving the mechanism of xanthomatous cells in meningioma, the positivity of histiocytic markers does not always mean histiocytic differentiation. CD68 positivity may indicate metabolic abnormality associated with histogenesis in xanthomatous meningioma, besides it may reflect the presence of abundant lysosomes in the cytoplasm of the xanthomatous cells.[7812] Liu et al.[15] could not clarify whether histiocytic infiltration is neoplastic or inflammatory in their case; therefore, they proposed the term “histiocytic meningioma.” They argued that it may classify separately because not all histiocytes in this tumor have the same biological features as meningothelial cells. For confirming this, electron microscopy is necessary; however, no electron microscopy was done in our case. Xanthomatous cells have also been reported to be positively stained with adipophilin.[811] Adipophilin demonstrates cells containing lipid droplets.[16] Ishida et al.[8] observed adipophilin positivity in both xanthomatous and conventional areas, while Ersoz et al.[11] only observed it in xanthomatous areas.

Xanthomatous changes manifest focally or diffusely and occur alone or in combination with other mesenchymal components.[2] Roncaroli et al., in their study regarding lipomatous meningiomas, reported 6 cases of xanthomatous cells admixed with adipocyte-like cells.[6] As transitions between xanthomatous and lipomatous areas were found in some cases, the authors proposed the term “lipidized meningioma” for these lipid-containing tumors, both xanthic and lipoma-like. Besides having been observed together, lipomatous meningioma was included in the differential diagnosis of xanthomatous meningioma. Lipomatous meningioma is composed of meningothelial neoplastic cells with adipocyte-like cells.[13] These adipocyte-like cells contain large round, eccentrically located nuclei with large lipid vacuoles resembling mature adipocytes, in contrast to xanthomatous cells with central nuclei resembling histiocytes. In addition, these adipocyte-like cells have been reported to be stained with S100 positively.[17] As no lipoblast-like or adipocyte-like cells were observed in our case, S100 staining was not performed.

Another differential diagnosis is microcystic meningioma, which is another variant of grade I meningiomas. Its intercellular spaces sometimes mimic fat accumulation but contain edematous clear fluid collections surrounded by “cobweb-like” meningothelial neoplastic cells.[1] Moreover, the neoplastic cells of microcystic meningiomas are EMA positive and CD68 negative. Clear cell meningioma, which has clear cytoplasm caused by glycogen accumulation, also resembles xanthomatous meningioma, but due to its prominent interstitial and perivascular hyalinization and PAS positivity, it is distinguishable. In our case, there was no interstitial and perivascular hyalinization and xanthomatous cells showed no PAS positivity.

In differential diagnosis, it should be distinguished from intracranial histiocytic disorders such as Rosai–Dorfman disease (RDD). RDD is composed of a mixed infiltrate that often includes plasma cells, histiocytes (positive for CD68 and S100 protein, negative for CD1a), and lymphocytes. Emperipolesis is present in most of the cases. With the presence of foamy stromal cells, hemangioblastoma also may be morphologically mistaken with xanthomatous meningioma. The foamy stromal cells commonly show degenerative nuclear atypia and express inhibin alpha and brachyury by immunohistochemistry.

CONCLUSION

This report presents a rare case of xanthomatous meningioma diagnosed based on its characteristic xanthomatous changes. As its differential diagnosis includes grade II clear cell meningioma, RDD, and hemangioblastoma, a high degree of awareness of this unique subtype of meningioma is required for making a correct diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the Journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Peer review

This article was peer-reviewed by two independent and anonymous reviewers.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.