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| Year : 2014 | Volume
: 57
| Issue : 2 | Page : 183-186 |
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| Secretory meningioma: A diagnostic pitfall |
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Ruchita Tyagi1, Rakesh Kumar Vasishta1, Nandita Kakkar1, Bishan Dass Radotra1, K. K. Mukherjee2
1 Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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| Date of Web Publication | 19-Jun-2014 |
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 Abstract | | |
Context: Secretory meningioma is a rare subtype of meningiomas, displaying epithelial and secretory differentiation of meningothelial cells. It has unique radiological, morphological, and immunohistochemical features, but runs a benign course. Radiological picture because of the variable degrees of peritumoral edema can be confused with aggressive neoplasms. Morphologically, it is difficult to distinguish secretory meningioma from other tumors having a clear cell appearance and aggressive clinical behavior. Materials and Methods: Retrospective analysis over a period of 16 years (1997-2012) brought out five cases diagnosed as secretory meningioma. The slides were restained and subject to special stains and immunohistochemistry and the clinical details were retrieved. Results: On histopathology, the tumors showed a characteristic vacuolated appearance due to the presence of variably sized intracytoplasmic lumina. Another unique feature was the presence of hyaline inclusions within these intracytoplasmic lumina and in the intercellular spaces. These inclusions were periodic acid-Schiff positive diastase-resistant, yellowish-orange on Elastic Van Giesson stain and strongly carcinoembryonic antigen positive. Conclusion: Owing to its rarity and unique morphology secretory meningioma poses a diagnostic challenge to the pathologists. As this tumor follows a benign course, it is crucial to correctly diagnose this entity to avoid unnecessary over treatment. Keywords: Carcinoembryonic antigen, hyaline inclusions, secretory meningioma
How to cite this article:
Tyagi R, Vasishta RK, Kakkar N, Radotra BD, Mukherjee KK. Secretory meningioma: A diagnostic pitfall. Indian J Pathol Microbiol 2014;57:183-6 |
| Introduction | |  |
Meningiomas are slow growing, extracerebral brain tumors and exhibit a wide variety of morphological patterns due to pluripotent nature of arachnoid cap cells, which are presumed to be the cell of origin of meningiomas. [1] WHO has described 15 subtypes of meningiomas and has graded them as meningioma, atypical meningioma and anaplastic meningioma, according to increasing biologic behavior clinically. [2] Secretory meningioma, with incidence of 1.2-9.3%, demonstrates epithelial and secretory differentiation of meningothelial cells. [3],[4] This tumor is a diagnostic pitfall for the pathologists. The characteristic histological feature is presence of numerous large intracytoplasmic vacuoles, which push the nuclei of meningothelial cells to one side, giving the appearance of a clear cell tumor and causes a diagnostic dilemma. These intracytoplasmic vacuoles contain hyaline globules, which are periodic acid-Schiff (PAS) positive and diastase-resistant. The whorling pattern of meningothelial cells, which is the typical morphological feature of meningiomas may be present focally and has to be looked for by taking multiple sections. Despite being a Grade I meningioma, it causes marked brain edema, a feature commonly seen with aggressive malignant intraparenchymal brain tumors. [3],[5]
Secretory meningioma is a rare tumor, which has unique histopathological, immunohistochemical features and displays benign biological course. Hence, it is important to correctly diagnose this lesion. We present collection of five cases diagnosed as secretory meningioma in our tertiary care institute, over a period of 16 years.
| Materials and Methods | | |
Retrospective analysis over a period of 16 years (1997-2012) brought out 5 cases diagnosed as secretory meningioma out of 1000 cases of meningioma (incidence 0.5%). The slides were restained and subject to special stains and immunohistochemistry and the clinical details were retrieved. The data collected included age, gender, radiological findings, location of the tumor, and histopathological findings. The paraffin embedded tissues were restained with Hematoxylin and Eosin. Special stains like PAS with and without diastase, Elastic Van Gieson (EVG) and immunohistochemical stains for carcinoembryonic antigen (CEA), vimentin, and epithelial membrane antigen (EMA) using Dako antibodies were performed.
| Results | | |
Clinical details
The age ranged from 35 to 77 years, (mean age 48.2 years) with a female preponderance (female to male ratio of 4:1). [Table 1]. The symptoms included headache, unilateral weakness of body, seizures, and loss of consciousness. On examination, papilledema, hemiparesis and nerve palsies were commonly present. Computed tomography and magnetic resonance imaging showed variable sized supratentorial, intracranial, axial or paraxial space occupying lesions, which were dura-based and displayed varying degrees of peritumoral cerebral edema, [Figure 1]. The largest dimensions noted, on radiology, were 6.7 cm x 6 cm x 5.7 cm in a 35-year-old-male patient. | Figure 1: T1-weighted axial plain (a) and contrast (b) Magnetic resonance imaging reveals a multiseptate solid cystic mass with enhancement of periphery and the septae. (c) T2-weighted image shows mild edema
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 | Table 1: Clinical data and microscopic features of cases of secretory meningioma
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Histopathology
On gross inspection, the specimens comprised predominantly of irregular tissue pieces. The size of the specimens ranged from 1 to 8 cm (case no. 2). No necrosis or hemorrhage was noted grossly. On microscopic examination, all the tumors were composed predominantly of sheets of tumor cells having a vacuolated appearance due to the presence of variably sized intracytoplasmic lumina, which had pushed the nuclei of the cells to one side. This imparted a clear cell appearance to the tumors. [Figure 2]. The characteristic whorling pattern normally seen in meningiomas was seen focally in two cases only. Necrosis, nuclear atypia and increased mitotic activity were absent. Ki-67 labeling index was <4%. All the cases showed the presence of variable sized, eosinophilic hyaline inclusions within the intracellular lumina as well as extracellularly. The eosinophilic inclusions were strongly PAS positive diastase-resistant, stained yellowish-orange with EVG and strongly positive for CEA. [Figure 3]. The vacuolated cells however showed immune positivity with CEA, EMA and vimentin. The variably sized intracytoplasmic lumina containing CEA and PAS positive eosinophilic hyaline inclusions helped us to arrive at the diagnosis of secretory meningioma thereby excluding other tumors with a clear cell appearance in this location, namely, clear cell meningioma, microcystic meningioma, chordoid meningioma, and metastatic mucin secreting/clear cell adenocarcinoma. | Figure 2: Sheets of tumor cells having vacuolated appearance due to variable sized intracytoplasmic lumina containing hyaline inclusions. (H and E, x200)
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 | Figure 3: (a) H and E stain showing intracellular and extracellular eosinophilic hyaline inclusions. (b) which are periodic acid-Schiff positive (c) and yellowish-orange on Elastic Van Giesson (d) Strong carcinoembryonic
antigen positivity in tumor cells and the hyaline inclusions
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| Discussion | | |
Secretory meningioma, with incidence of 0.5% in our institute, is a rare subtype of meningioma. Other studies have reported incidence ranging from 1.2 to 9.3%. [3],[4] Cushing and Eisenhardt termed the secretory globules as "glassy hyaline inclusions," while Kepes called them "pseudopsammoma bodies" and described that they lack reticulin or collagen fibers and do not undergo calcification. [6] Finally, the term -" secretory meningioma " was coined by Alguacil-Garcia et al. in 1986, after confirming the unique secretory characteristics of this subgroup of meningiomas. [7]
Secretory meningiomas exhibit a female predilection as also seen in four of the five cases in our study. The sites most commonly affected are frontal convexity and sphenoid ridge. [3],[8] In this study, two cases were seen in the frontal lobes, one each in the sphenoid, parietal, and parafalcine region. Various hypotheses have been proposed to explain brain edema in meningiomas. According to cerebral compressive theory, larger tumors cause more brain compression than smaller tumors and this may lead to ischemia, necrosis, or secondary edema formation. [9],[10] However, Probst-Cousin et al. did not find any correlation between tumor size and edema. [3] Vascular compressive theory proposes that meningiomas present in locations, which cause occlusion of major cerebral veins and compression of dural sinuses, may cause venous stasis and secondary fluid extravasation into interstitial brain space. Inamura et al. have found meningiomas situated in frontal region and sphenoid ridge tend to be more commonly associated with peritumoral edema. [11] Probst-Cousin et al. also could not exclude the influence of tumor location on edema formation. [3] According to Bitzer et al., meningiomas displaying vascular endothelial growth factor (VEGF) expression were associated with peritumoral edema. VEGF secretion may increase the permeability of cerebral vessels, leading to edema in adjacent areas. [12] Brain edema is generally seen in more aggressive, fast growing, malignant, and intraparenchymal tumors. Secretory meningioma, being an extracerebral, slow growing Grade I benign tumor has the propensity to cause variable degrees of brain edema, leading to diagnostic dilemma for the clinician as well as the radiologists. [10] Variable degrees of peritumoral edema were seen in all of our five cases.
On histopathology, the morphology of secretory meningioma differs from that of usual meningiomas due to paucity of whorling pattern generally associated with meningiomas. The diagnostic challenge is further accentuated by the vacuolated appearance of tumor cells caused by the presence of variably sized intracellular lumina, which push the nuclei of the tumor cells to the periphery, giving a clear cell appearance. Another unique morphological feature of secretory meningioma is the presence of hyaline inclusions/hyaline globules, also known as pseudopsammoma bodies, within the intracytoplasmic lumina and in the extracellular spaces. True psammoma bodies are not seen. These hyaline inclusions stain yellowish-orange with EVG stain. The cells immunostain positively with CEA, EMA, and vimentin. This further establishes the epithelial differentiation of secretory meningiomas. [7],[8],[13],[14],[15] Patients with secretory meningiomas have also been found to have raised serum CEA levels. [8],[16],[17]
Morphologically, secretory meningioma needs to be differentiated from microcystic/clear cell/chordoid meningiomas, which resemble secretory meningioma in that they all have a clear cell appearance due to intracellular or extracellular vacuoles and/or mucoid substances. Microcystic meningioma shows cells with thin elongated processes encompassing multiple pale to optically clear microcysts that may contain PAS-positive, diastase-resistant fluid. Clear cell meningiomas have a predilection for cerebellopontine angle and cauda equine region, unlike secretory meningiomas, which usually occur in frontal convexity and sphenoid wing. Clear cell meningioma also shows cells which are PAS positive, but diastase sensitive due to the presence of glycogen arranged in vague whorling pattern. Chordoid meningioma displays clusters, cords, and trabeculae of polygonal, eosinophilic or vacuolated cells in a mucoid matrix ("chordoid" architecture). However, PAS-positive diastase-resistant CEA positive hyaline globules are a unique characteristic of secretory meningiomas and help to distinguish them from other subtypes of meningiomas. This distinction is important as chordoid meningioma and clear cell meningioma have an aggressive behavior with a high propensity for recurrence. [2] Due to its clear cell morphology, secretory meningioma may sometimes resemble metastatic mucin secreting/clear cell adenocarcinoma. However, clinicoradiological details and the PAS and CEA positive hyaline globules help to clinch the diagnosis.
| Conclusion | | |
Secretory meningioma is an unusual type of meningioma with unique radiological, histological, and immunohistochemical features. Due to its rarity, secretory meningioma poses a diagnostic challenge for the pathologists. Even though, it causes variable degrees of peritumoral edema, it follows a benign course. Hence, it is important to diagnose it correctly and distinguish it from more aggressive and malignant tumors of the brain to avoid unnecessary overtreatment.
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Correspondence Address:
Nandita Kakkar
Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0377-4929.134659
[Figure 1], [Figure 2], [Figure 3]
[Table 1] |
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