9530/0 - Secretory meningioma
C70, C71 and C72 - Tumours of the central nervous system


Definition

A benign (WHO grade I) histological variant of , histologically characterized by focal epithelial differentiation presenting as intracellular PAS positive pseudopsammoma bodies rich in glycogen, with immunoreactivity for epithelial membrane antigen (EMA) and cytokeratin 1 .

Epidemiology

Epidemiological data are based on clinical series, the largest of them comprising 44 2 and 31 3 cases. 3 % of meningiomas were reported to be secretory 4 5 , ranging from 1.6 6 to 9.3 % 7 . There is female preponderance of 8:2 8 or more 9 , in smaller samples there may be only female cases 10 . The prevalence must be seen in relation to meningiomas in general (see ; the female predisposition exceeds the rate of most other meningioma subtypes.

Localization

Secretory meningioma are frequently located at the sphenoid ridge and at the frontal convexity but have been also seen on other regions at the convexity, the cranial base, cerebellopontine angle and clival region.

Signs

Secretory meningiomas are characterized by a female predominance (female/male ratio of 8:1) which differ from the overall group of meningiomas. This feature may be supported by the finding that secretory meningiomas show high rates (33-100%) of progesterone and estrogen receptors. Age (mean 58 years) does not differ from other meningioma patients.

Imaging

A massive peritumoral edema is the striking feature of secretory meningiomas while the tumor itself presents simliar to the overall group of meningiomas. On CT-imaging contrast enhancing and well demarcated lesions are diagnosed. Peritumoral edema may be smaller than the tumor size, exceeding the tumor size or may invlove the entire hemisphere. The extent of edema is best diagnosed on T2-weighted MR-images and should be correlated to the tumor size. Homogenous enhancement of the tumor itself and dural attachment in some cases are not differing from other meningiomas. But a nearly hemispheric edema will most likely correspond to the diagnosis of a secretory meningioma which is not seen in other meningiomas in a similar location or size.

Macroscopy

The gross aspect of secretory meningioma does not differ from other meningiomas.

A peculiar feature often observed is the production of abundant peritumorous edema in contrast to meningioma in general (see ). This may erroneously be thought to indicate malignancy. Single case reports 11 are mostly induced by the observation of the discrepancy between severe perifocal edema and the basically benign nature of the lesion.

Histopathology

Secretory meningiomas contain cell complexes, that group around intracytoplasmic inclusions, round or fragmentated PAS-positive droplets. They are the hallmark of this entity, named “hyaline inclusion bodies” 12 , or “pseudopsammoma bodies” 13 .

Otherwise, secretory meningioma presents the histological features of the meningioma entity (see and pertinent subgroups). Often a rather loose cellular arrangement prevails indicating higher fluid content of the tumor. This leads to the denomination of cystic 14 or microcystic-secretory 15 . Thus, it seems not impossible that the secretory and microcystic variants are interdependent.

There is an increase of mast cells within these tumors 16 . In some tumors there is association of the prominent vasculature with mast cells and the secretory globules containing complexes. Since mast cells are known to be vasoactive, they may induce the high amount of vessels, which in turn may cause the perifocal edema.

Electron microscopic investigations confirmed the secretory nature of the pseudopsammoma bodies 17 . Ultrastructurally, the secretory droplets are osmiophilic products occuring as compact or fragmentated masses within holes, that are rimmed by the cell membrane with microvilli protruding into the lumen between cell membrane and secretory mass. Mast cells can be identified by their cytoplasmic granulation. The remaining ultrastructural features are those occurring in other meningiomas.

Characteristic features of secretory meningioma displayed by the PAS reaction: Hyaline bodies or pseudopsammoma bodies as compact droplets (middle) or as fragmentated inclusions (left). In addition, mast cells (right lower part) are depicted. Note nuclear indentations in many cell nuclei.Ultrastructurally, pseudopsammoma bodies are compact masses within a cytoplasmic hole (right) or multiple fragments of varying electron densities (left). The holes are lined by membranes that form microvilli prodruding into the lumen.Mast cells by electron microscopy are characterized by their content of dark granules (left). These cells are often observed next to tumor vessels; here a capillary surroundet by two mast cells is displayed.

Immunoprofile

The imunoprofile of the secretory variant is that of meningioma with additional features concerning secretory complexes, mast cells and pericytic proliferations. The complexes that contain pseudopsammoma bodies exhibit immunoreactivity for epithelial membrane antigen (EMA) as well as for different cytokeratins 18 , especially stratifying cytokeratin 5 and 6, variably for cytokeratine 7, 8, never for cytokeratine 20 19 . By combined application of the cytokeratin reaction and PAS staining, an association of vasculature and secretory complexes may be demonstrated. Carcinoembryonic antigen (CEA) is equally expressed in these formations 20 . Mast cells may be visualized by the immunorection with CD-117 and their granular content, e.g. serotonin.

The occurrence of both secretory complexes and usual meningioma formations, mostly meningothelial, prompted unusual investigations and results. Thus Merlin has been demonstrated in both features 21 , whereas female sex hormone receptors occur in the non secretory parts 22 . There may be even be elevated serum level of CEA 23 . CD 44 variants are found in pseudopsammoma bodies 24 , as well as carbohydrate antigen 19-9 and different immunoglobulins 25 . Ubiquitin and Alpha-1-Antitrypsin obviously occurred in secretory bodies and surrounding parts 26 . The proliferated vessels may be visualized by pertinent immunoreactions.

Pseudopsammoma body containing complexes are cytokeratin reactive (brown islands) and are localized in close connection to tumor vessels (light PAS positive). The pseudopsammoma bodies stain dark red in a combined application of the PAS reaction and cytokeratin immunohistochemistry.

Grading

Secretory meningiomas are generally considered to have low proliferation activity, the MIB labeling index being 3% 27 or less 28 , ranging from 0 to 17% 29 . Secretory meningiomas correspond to WHO grade I 30 . One case only with recurrence and malignant transformation has been published 31 .

Therapy

Complete surgical resection is the goal of treatment but may be limited in some cases due to infiltration of the cavernous sinus or other eloquent regions. Resection is significantly more often accomplished in tumors of the convexity than in tumors located at the base of the brain. The postoperative course in about two thirds of the cases is uneventful and does not require a special postoperative care.
But some patients suffer from progressive neurological symptoms or even loss of consciousness during the postoperative period. Perifocal edema exceeding the tumor size or reaching nearly hemispheric size are seen in all of these patients already preoperatively. Increasing edema and mass effect necessitates aggressive anti-edematous therapy with respirator assisted ventilation and intracranial pressure (ICP) monitoring for several days postoperatively. Patients age and location of the tumor do not correlate to the clinical course.


Prognosis

In secretory meningioma a suspicious disproportion between small tumor size and extended perifocal edema is observed which may justify an aggressive anti-edematous therapy already before surgery in order to prevent postoperative aggravation of edema. Predictive factors seemed to be only female gender and nearly hemispheric edema while the tumor itself remains unsuspicious compared to the overall group of meningiomas. Awareness in the clinical course enables the postoperative caregivers to brace for extended sedation, and anti-edematous therapy and a lower threshold for postoperative imaging. Apart from this acute peri-operative problem secretory meningiomas show a prognosis comparable to other benign meningiomas.


1Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds.), WHO Classification of Tumours of the Central Nervous System., 4th Edition, International Agency for Research on Cancer, Lyon 2007
2Regelsberger J, Hagel C, Emami P, Ries T, Heese O, Westphal M (2009) Secretory meningiomas: a benign subgroup causing life-threatening complications. Neuro Oncol 11: 819-24
3Probst-Cousin S, Villagran-Lillo R, Lahl R, Bergmann M, Schmid KW, Gullotta F (1997) Secretory meningioma: clinical, histologic, and immunohistochemical findings in 31 cases. Cancer 79: 2003-15
4Regelsberger J, Hagel C, Emami P, Ries T, Heese O, Westphal M (2009) Secretory meningiomas: a benign subgroup causing life-threatening complications. Neuro Oncol 11: 819-24
5Probst-Cousin S, Villagran-Lillo R, Lahl R, Bergmann M, Schmid KW, Gullotta F (1997) Secretory meningioma: clinical, histologic, and immunohistochemical findings in 31 cases. Cancer 79: 2003-15
6Colakoğlu N, Demirtaş E, Oktar N, Yüntem N, Islekel S, Ozdamar N (2003) Secretory meningiomas. J Neurooncol 62: 233-41
7Alguacil-Garcia A, Pettigrew NM, Sima AA (1986) Secretory meningioma. A distinct subtype of meningioma. Am J Surg Pathol 10: 102-11
8Regelsberger J, Hagel C, Emami P, Ries T, Heese O, Westphal M (2009) Secretory meningiomas: a benign subgroup causing life-threatening complications. Neuro Oncol 11: 819-24
9Tirakotai W, Mennel HD, Celik I, Hellwig D, Bertalanffy H, Riegel T (2006) Secretory meningioma: immunohistochemical findings and evaluation of mast cell infiltration. Neurosurg Rev 29: 41-8
10Buhl R, Hugo HH, Mihajlovic Z, Mehdorn HM (2001) Secretory meningiomas: clinical and immunohistochemical observations. Neurosurgery 48: 297-301; discussion 301-2
11Tsuzuki N, Nakau H, Sugaya M, Hashizume K, Matsukuma S, Wada R, Kuwabara N (1997) Secretory meningioma with severe perifocal edema--case report. Neurol Med Chir (Tokyo) 37: 620-3
12Cushing, H., Eisenhardt, L, Meningiomas Their Classification, Regional Behaviour, Life History and Surgical End Results, Charles C Thomas, Illinois 1938
13Kepes, J.J., Observations on the formation of psammoma bodies and pseudopsammoma bodies in meningiomas, Journal of Neuropathology and Experimental Neurology. 20:255-262, 1961
14Mennel HD, Arndt D, Plate KH, Bauer BL (1989) Cystic meningioma with unusual histopathological features. Virchows Arch A Pathol Anat Histopathol 416: 169-75
15Regelsberger J, Hagel C, Emami P, Ries T, Heese O, Westphal M (2009) Secretory meningiomas: a benign subgroup causing life-threatening complications. Neuro Oncol 11: 819-24
16Tirakotai W, Mennel HD, Celik I, Hellwig D, Bertalanffy H, Riegel T (2006) Secretory meningioma: immunohistochemical findings and evaluation of mast cell infiltration. Neurosurg Rev 29: 41-8
17Kepes JJ (1975) The fine structure of hyaline inclusions (pseudopsammoma bodies) in meningiomas. J Neuropathol Exp Neurol 34: 282-94
18Miettinen M, Paetau A (2002) Mapping of the keratin polypeptides in meningiomas of different types: an immunohistochemical analysis of 463 cases. Hum Pathol 33: 590-8
19Tirakotai W, Mennel HD, Celik I, Hellwig D, Bertalanffy H, Riegel T (2006) Secretory meningioma: immunohistochemical findings and evaluation of mast cell infiltration. Neurosurg Rev 29: 41-8
20Alguacil-Garcia A, Pettigrew NM, Sima AA (1986) Secretory meningioma. A distinct subtype of meningioma. Am J Surg Pathol 10: 102-11
21Buccoliero AM, Gheri CF, Castiglione F, Ammannati F, Gallina P, Taddei A, Garbini F, Degl'Innocenti DR, Arganini L, Di Lorenzo N, Mennonna P, Taddei GL (2007) Merlin expression in secretory meningiomas: evidence of an NF2-independent pathogenesis? Immunohistochemical study. Appl Immunohistochem Mol Morphol 15: 353-7
22Li XJ, Zhang HY, Lang ZQ, Wei B, Chen HJ, Bu H (2006) [Analysis of clinical and pathological features of secretory meningiomas] Sichuan Da Xue Xue Bao Yi Xue Ban 37: 488-91
23Louis DN, Hamilton AJ, Sobel RA, Ojemann RG (1991) Pseudopsammomatous meningioma with elevated serum carcinoembryonic antigen: a true secretory meningioma. Case report. J Neurosurg 74: 129-32
24Suzuki SO, Iwaki T, Kitamoto T, Mizoguchi M, Fukui M, Tateishi J (1996) Differential expression of CD44 variants among meningioma subtypes. Clin Mol Pathol 49: M140-6
25Probst-Cousin S, Villagran-Lillo R, Lahl R, Bergmann M, Schmid KW, Gullotta F (1997) Secretory meningioma: clinical, histologic, and immunohistochemical findings in 31 cases. Cancer 79: 2003-15
26Colakoğlu N, Demirtaş E, Oktar N, Yüntem N, Islekel S, Ozdamar N (2003) Secretory meningiomas. J Neurooncol 62: 233-41
27Regelsberger J, Hagel C, Emami P, Ries T, Heese O, Westphal M (2009) Secretory meningiomas: a benign subgroup causing life-threatening complications. Neuro Oncol 11: 819-24
28Tirakotai W, Mennel HD, Celik I, Hellwig D, Bertalanffy H, Riegel T (2006) Secretory meningioma: immunohistochemical findings and evaluation of mast cell infiltration. Neurosurg Rev 29: 41-8
29Regelsberger J, Hagel C, Emami P, Ries T, Heese O, Westphal M (2009) Secretory meningiomas: a benign subgroup causing life-threatening complications. Neuro Oncol 11: 819-24
30Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds.), WHO Classification of Tumours of the Central Nervous System., 4th Edition, International Agency for Research on Cancer, Lyon 2007
31Shivane AG, Chakrabarty A, Baborie A, Thiryayi W, Donaldson MH, Ross S (2006) A rare case of recurrent secretory meningioma with malignant transformation. Br J Neurosurg 20: 250-3