Whorling-Sclerosing Meningioma. a Review on the Histological Features of a Rare Tumor Including an Illustrative Case

Clinical Neurology and Neurosurgery 162 (2017) 85–90

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Clinical Neurology and Neurosurgery

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Review Article Whorling-sclerosing meningioma. A review on the histological features of a MARK rare tumor including an illustrative case ⁎ İlhan Elmacia, Meric Adil Altinoza, , Aydin Savb, Fatih Han Bolükbaşıa, Mustafa Önöza, Özdil Başkana, Ramazan Saria a Neuroacademy Research Group, Memorial Hospital, Department of Neurosurgery, Kaptanpasa Mh, Okmeydani/Sisli, Istanbul, 34384, Turkey b Nisantasi Pathology Laboratories, Sisli, İstanbul, Turkey

ARTICLE INFO ABSTRACT

Keywords: Whorling-Sclerosing variant of meningioma (WSM) is a very rare variant of meningioma and only 28 cases were Whorling sclerosing meningioma previously reported in the English medical literature. The term “whorling” describes different morphological Histology features including psammoma bodies formed by precipitated calcium or by layered whorling sheets of tumor Histochemistry cells in meningothelial meningiomas. In WSM, the sclerosing structures are formed by typical paucicellular or Differential diagnosis acellular collagen whorls which form the majority of tumor volume. Hence, diagnosis of these tumors is based more often on morphological and histochemical features rather than on immunohistochemical findings. WSMs often contain cells with both fibroblast-like spindle cell morphology predominantly immunopositive for vimentin and meningoepithelial cells immnunopositive for EMA. The range of their Ki-67 indices differs between 0 and 4 percent. These tumors show no focal pleomorphism, necrosis and high mitotic activity. In some WSMs, entrapped GFAP immunopositive astrocytes may be seen during invasion of the adjacent neural parenchyma. Brain invasion by WSMs may give rise to erroneous diagnoses, i.e. malignant (Grade-3) meningioma, me- ningiosarcoma, ganglioglioma and even astrocytoma, leading detrimental overtreatment. However; hitherto, no WSM was reported exerting any aggressive behavior. Besides reviewing the literature, we also report a new WSM with abundant uncalcified paucicellular collagen whorls forming aggregates of nodules. Unlike to previous reports, this tumor was costained with p53 and progesterone receptor. The tumor showed no morphological malignancy characteristics, e.g. cellular atypia, prominent nucleoli, hypercellularity, micronecrosis/geographical necrosis, sheeting and small cells. This rare meningioma variant should be kept in mind among differential diagnoses to avoid overtreatment that might endanger patients’ outcome.

1. Introduction is used to define different morphological features including psammoma bodies formed by precipitated calcium and whorling sheets of tumor Meningioma is a neoplasm of meningeal cap cells and it accounts cells in meningothelial meningiomas. Eye-catching whorling and about 30% of all intracranial tumors [7]. Meningothelial, fibroblastic sclerosing structures are formed by paucicellular zones or acellular and transitional meningiomas are the most common subtypes of me- collagen, which are the characteristic features of WSM. WSMs follow an ningioma in the WHO classification. Less common subtypes are meta- indolent behavior. Therefore, distinguishing WSM’s from other high plastic (lipomatous, osseous, cartilaginous, myxoid, xanthomatous), grade tumors is important to avoid erroneous decisions leading to psammomatous, secretory, angiomatous, lymphoplasmacyte-rich and chemotherapy or radiotherapy, adversely effecting mental development microcystic meningiomas. In 1989, a histologic subtype of me- especially in children. In this report, we present a rare case of WSM ningiomas was described by Davidson et al., which has not previously which has some additional features which were not described in earlier been defined [2]. In these tumors, viable cells constituted only a small reports. Thereafter, we review the available literature by analyzing and portion of the lesion, most of which have little appearance of conven- comparing immunohistochemical markers separately, which was not tional meningothelial cells [2]. The bulk of the lesions consisted of performed previously for this type of meningioma. whorling collagen bundles. [2] Later, the same tumor was also named as “whorling sclerosing meningioma – WSM” [4]. The term “whorling”

⁎ Corresponding author at: Guven Sk. Yildirim Apt. No:5 Kagithane, Istanbul, Turkey. E-mail address: [email protected] (M.A. Altinoz). http://dx.doi.org/10.1016/j.clineuro.2017.09.009 Received 14 June 2017; Received in revised form 15 September 2017; Accepted 25 September 2017 Available online 28 September 2017 0303-8467/ © 2017 Elsevier B.V. All rights reserved. İ . Elmaci et al. Clinical Neurology and Neurosurgery 162 (2017) 85–90

Fig. 1. (A) Axial and (B) coronal T2-weighted images show a mass (arrows) which is isointense to gray matter, involving left cavernous sinus and invading the Meckel cave and the pituitary gland. (C) Coronal postcontrast T1-weighted image shows a homogeneously enhancing mass.

® 1.1. Clinical description of the index case receptor ((PGR-312, Novocastra ) recognizes N-terminal region of the A form of the human progesterone receptor), 2- CD45 (LCA – leukocyte ® ® A 37-years old women patient was admitted with complaints of common antigen, PD7/26/162B1, Scytek ), 3- Ki67 (MIB-1, Dako ), 4- ® tiredness, diplopia and sense of pulling of her left leg. Magnetic re- EMA (Epithelial Membrane Antigen, E29, Neomarkers – Delipidated sonance imaging (MRI) of the brain (Fig.1) revealed a nodular mass extract of human milk fat globule membranes was used as immunogen ® involving the left cavernous sinus extending to the Meckel cave and the to obtain anti-EMA antibodies), 5- p53 (DO/7, Scytek , its epitope maps ® pituitary gland. The mass was isointense to gray matter in T2- and T1- within the N-terminus (aa 37–45) of p53, 6- CD34 (QBend/10, Scytek , weighted images and enhanced homogeneously in postcontrast T1- reacts with a 110 kD glycoprotein, present on the surface of hemato- weighted images. Her complaints alleviated under steroid treatment; poietic cells, i.e. myeloid and lymphoid progenitors.), 5- Vimentin (V9, ® yet due to the progression observed on follow-up MRI’s, she was hos- Scytek , recognizes a 57–60 kDa protein which is identiﬁed as a me- ® pitalized for the surgical excision of the tumor. During surgery, a left senchymal marker), 6- S100 (4c4.9, Scytek ). 7- Pancytokeratin ® pterional craniotomy was performed and the Meckel cave lesion was (5D3LP34, Scytek , stains cytokeratins of 5/6/8/18). approached under neuronavigation and neuromonitorization. A mi- Table. 1 depicts the immunoreactivity scores of the each employed croscopical excision was performed with the guidance of intraoperative marker and also the ﬁndings of previous reports pertinent to this tumor. ultrasonography. A grey-yellowish, vascularized tumor localized in the S100 was intensely 4+ positive in the meningothelial area (Fig. 3b). left cavernous sinus with a good cleavage was spotted and easily aspi- Pancytokeratin (5/6/8/18) was intensely (+positive) in the sclerosing rated with suction. Its gross appearance was consistent with chondroid area (Fig. 3c). CD45 (LCA, leukocyte common antigen) was 2+ positive and soft tissue-like features with a size of 1,5 × 1 × 1 cm. No trans- (Fig. 3d). p53 was highly +3 positive (Fig. 4a). Progesterone receptor fusion was needed during surgery and no complication was evident was intensely 4+ positive (Fig. 4b). Additionally, further results were during the postoperative period. Her complaints were almost com- obtained which were not shown on photomicrographs: Ki67 index was pletely diminished and her condition is stable with no disease pro- 3.7% (min 1.4%, max 6.7%; Dako (MIB-1)), EMA was highly (3+) gression for 7 months. positive. CD34 was highly (+3) positive. Vimentin was intensely (4+) positive in the meningothelial areas and moderately (2+) positive in 1.2. General microscopical and histochemical features of the tumor the sclerotic portion.

On microscopical examination, acellular whorls formed onion-skin- 1.4. Review of the literature and discussion of the index case like layers consisting of collagen fibers. Periphery of the acellular fi sclerosing whorls were surrounded by meningothelial and broblast- As forementioned, WSMs were first described by Davidson et al., like spindle cells. Widespread blood vessels with mural hyalinization, when they analyzed pediatric meningeal tumors over a period of 18 fi stromal hyalinization and lymphocytic in ltration were detected. years [2]. They found that among 22 meningioma cases, 7 exerted Psammoma and pseudopsammoma bodies were not seen. No evidence sclerosing morphology; meaning that the bulk of the lesions consisted of of cellular atypia was observed including hypercellularity, micro- whorling collagen bundles. Furthermore, all cases in which there was a necrosis/geographical necrosis, sheeting, small cells and prominent brain invasion fell to this group of tumors [2]. Brain invasion coexisting fi nucleoli. Mitotic index was less than 4%/HPF (high power eld). with the “clear” cells and focal hypercellularity, and the reputation of Conventional histochemistry revealed diastase-resistant PAS-positive childhood meningiomas for malignancy caused false diagnoses when regular capillary basal membranes around the sparse vessels. Masson- the lesions were first seen [2]. Only 1 of their 7 cases had an original fi Trichrome stain for collagen bers and gomori silver impregnation for diagnosis of sclerosing meningioma. 2 of these were previously diag- fi fi reticulum bers revealed widespread collagen and reticulum bers in nosed as atypical, 1 malignant and 1 transitional meningioma. Last 2 – sclerosing whorls (Figs. 2 a d and 3 a). cases were diagnosed as meningeal sarcoma. Subsequently, 3 cases underwent radiotherapy and one received chemotherapy. However, it 1.3. Applied immunohistochemical antibodies and obtained findings was later found that prognosis for sclerosing meningiomas was similar to conventional meningiomas [2]. Immunohistochemistry (IHC) studies were performed on paraffin Also, in the series of Kim et al., the unusual histopathology as well sections using Ventana Benchmark XT. Following antibodies were used as the unequivocal brain invasion led to erroneous diagnoses in all of to obtain a detailed analysis of tumor pathology: 1- Progesterone their 5 cases. The diagnoses run a spectrum of malignant meningioma,

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Fig. 2. Eye catching abundant whorls at low (A) and high power (B) magnification (scale bars reflect 1000 μm and 200 μm, respectively, H.E.). (C) Transition zone between the sclerosing nodule and cellular component (scale bar reflects 50 μm, H.E.) (D) Collagen-rich nodule as demonstrated with Masson Trichrome stain (scale bar reflects 100 μm). ganglioglioma, fibrous meningioma, fibrous nodule, and a plasma cell anaplasia in meningiomas [1]. Hence, p53 expressivity in our case granuloma [8]. The initial diagnosis of malignant (Grade-3) me- might be interpreted as a most probably a post-translational modifica- ningioma in one case was based on the brain invasion by the tumor [8]. tion of wild-type p53 but not a mutation. We will not expect an in- Fukushima et al. observed WSM-tumor invasion into the adjacent brain sidious worse prognosis for this adult patient. parenchyma [3]. Traditionally, diagnosis of malignant meningioma The most characteristic histological finding of WSM is extensive should be based on number of mitotic figures ( > 20/HPF) and/or collagen deposition. Hope et al. mentioned that WSM highly consists of frank anaplasia [8,10]. The sparse population of cells with little re- almost acellular collagen [5]. Pope et al. stated that the major patho- semblance to meningothelial cells in WSMs may also have caused false logical hallmark for WSM diagnosis is the great number of round solid diagnoses [8]. In our tissue samples, p53 was positively stained, yet we collagen accumulations of variable size that stain green by the Papa- do not assume that this can be a sign of malignancy, since the tumor nicolaou method, magenta with Giemsa stain and eosinophilic with lacked any histologic parameters compatible with malignancy. Fur- H&E [12]. Uncalcified extracellular collagen fibers varied greatly in thermore, expression of PR is a sign of well differentiation and lack of size and showed eosinophilia, which were surrounded by scattered

Fig. 3. (A) Reticulin stain (scale bar reflects 200 μm). (B) S100 positive areas surrounding sclerosing nodule (scale bar reflects 200 μm). (C) Pancytokeratin positivity adjacent to collagen nodule (scale bar reflects 200 μm). (D) CD45+ immunocytes surrounding the sclerosing nodule (scale bar reflects 100 μm).

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Table 1 Morphological and immunohistochemical features of WSM.

Reference No pt(s) Collagen Men. PNH Astroc. Ki-67 Vimentin EMA GFAP PR PanCK S-100 P53 CD34 Whorl whorl Simil.

Davidson et al 7 4+ g+ g+ g+ +7/7 −7/7 Hope et al 7 4+ g+ g+ 1+ – Haberler et al 2 4+ 1+, 4+ 1+ focal 1+,2+ –– 2+ Pope et al 1 4+ 4+ 4+ 2+ – Kim et al 5 4+ g+ g+ < 0.1% 4+ − spin. −,+ spin. −,+ spin. –– İm et al 4 4+ g+ 0%–4% 4+ (spindle) −,1+ −,1+ –– Fukushima et al 1 4+ 2.4% 1+ –– – Perven et al 1 4+ ∼ 0% 1+ + – +Cyto Current Report 1 4+ g+ g+ – 3.67% 4+/2+ 3+ – 4+ 4+ 4+ 3+ 3+ (1.4–6.7%)

Abbreviations: No pt(s): Number of reported patients; Men Whorl: meningothelial cellular whorls; PNH: perinuclear halo; Astroc. Simil.: Morphological similarities to astrocytes with fibrillary extensions PR: Progesterone Receptor; spin. Spindle cells; PanCK: Pancytokeratin, CK: Cytokeratin; Numbers before the “+” sign show the positivity among the sample population, numbers after the “+” sign show the intensity of expression, g+: general presence, areas left blank: not specifically mentioned in the related manuscript. tumor cells [12].This was compatible with the typical features of our tumors varied [6].The majority of tumor cells in one case was round case specimen which included sclerosing acellular nodules rich in col- with clear cytoplasm, but had spindle morphology in two cases. In one lagen fibers surrounded by meningothelial and spindle cells. Kim et al. case, fibroblast-like and meningothelial cells were diffusely intervened suggested that in a total absence of meningothelial cells, paucicellular [6]. collagenous whorls were more diagnostic rather than im- Davidson et al. and Hope et al. reported that some cells in WSMs munohistochemistry [8]. According to Im et al., for a meningioma to be demonstrated perinuclear halos, causing a “fried egg” appearance [2,5]. diagnosed as WSM, at least 70% of the total tumor volume should Im et al. declared that spindle cells intervened with round cells of ‘fried consist of collagen whorls on the basis of four cases in their study [6]. egg’ appearance in WSMs [6].They also mentioned that these “fried In our case, nodules were predominantly composed of collagen fi- egg” cellular characteristics of WSMs are somewhat similar to those of a bers palizaded by meningothelial and spindle cells. There were no clear-cell variant, yet the former exerted profound stromal hyaliniza- psammoma and pseudopsammoma bodies but vascular and stromal tion replacing the greater part of tumor [6]. Since clear cell variant may hyalinization. Davidson et al. reported that the few cells in cellular be associated with a more aggressive biology [6]; Kim et al. suggested areas were mostly spindly and fibroblastic in appearance and lesser that prospective and retrospective long term follow-up is necessary to cells exerted meningothelial whorling [2]. Pope et al. found that tumor decide whether reminiscent clear cell meningiomas should be separated cells frequently enlaced around the collagenous whorls in a cap-like from WSMs [8]. The term “fried egg” is a morphological description fashion [12]. They also found that PAS-staining was negative within the identifying perinuclear clear cytoplasmic appearance surrounding a collagenous whorls and meningothelial whorls existed throughout the central nucleus with dense chromatin. Kim et al. proposed that the fried tumor [12]. They witnessed that cells had homogeneously eosinophilic egg appearance may be the result of hydropic degeneration [8]. In renal cytoplasm which lacked well-defined cell borders and contained round- cell carcinoma and clear cell meningioma, accumulation of PAS dia- to-oval nuclei with delicate chromatin. [12] Kim et al. found spindle stase stain-resistless material (glucose) may cause a similar appearance. cells with or without small foci of meningothelial cells in their WSM However; it shall be underlined that in the surgical neuropathology, the samples [8]. In the samples of Kim et al., the meningothelial cells “fried egg” description is not used to describe clear cell meningiomas formed small lobules in three cases; and in one case, tiny cellular but limited only for oligodendroglioma. In oligodendrogliomas, this clusters formed a meningioma reminiscent of clear cell variant also specific feature is accepted to be a regular repetitive artifact of tissue accompanied with progressive sclerosis [8]. Meningothelial cell pro- fixation. liferations commonly associated with psammoma bodies or whorls [8]. Davidson et al. reported that in the more cellular areas in WSMs, The spindle cells formed loose fascicular patterns in most tumoral areas, some cells with fibrillary extensions resembled astrocytes [2]. Kim et al. and focally showed vague whorl formations [8]. In one case, spindle also mentioned that some spindle cells in WSMs had elongated or club tumor cells and interspersed neurones at the brain invasion-sites mi- shaped nuclei and wavy cytoplasmic extensions, mimicking astrocytes micked ganglioglioma; but this tumor also displayed osseous, lipoma- or Schwann cells [8]. Glial fibrillary acidic protein (GFAP) is a reliable tous and xanthomatous changes, reminiscent of a metaplastic me- marker for normal, reactive, and neoplastic astrocytes and is the ningioma [8]. Im et al. also underlined that the morphology of these dominant component of glial intermediate filaments. More recently,

Fig. 4. (A) Nuclear p53 immunoreactivity adjacent to the sclerosing nodule (scale bar reﬂects 20 μm). (B) Nuclear progesterone receptor immunoreactivity next to the sclerosing nodule (scale bar reﬂects 100 μm).

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GFAP immunopositivity has been recognized in other tumors, including for vimentin [5]. Haberler et al. found numerous cells stained with papillary meningioma and renal cell carcinoma metastatic to brain vimentin in their two WSM samples [4]. Pope et al. declared that me- [11]. Davidson et al., Hope et al. and Fukushima et al. did not find ningioma cells showed diffuse cytoplasmic reactivity for EMA [12]. Kim GFAP expression in their WSM cases [2,3,12]. Haberler et al. obtained et al. also mentioned that the spindle cells in their 5 meningioma contradictory results regarding GFAP-expression in meningiomas with samples displayed a robust expression of vimentin [8]. Similarly, in the different antibodies; some antibodies revealed GFAP expression while WSM samples of Im et al., tumor cells exhibited positive reaction for some did not [4]. Perven et al. witnessed sparse GFAP-positive cells in vimentin in all cases [6]. an extensively hyalinized tumor [11]. According to some authors, ec- tomesenchymal origin of the human meninges from the neural crest 4. S100 protein might explain GFAP expression in some meningiomas [12]. However, others have proposed that GFAP-positive cells are entrapped astrocytes S100 is a calcium binding protein, which is expressed both on cell during invasion of WSMs into the surrounding brain tissues, which may membranes and in cell nuclei. There is a wide cellular repertoire which also cause an incorrect diagnosis of a glioneuronal neoplasm, i.e. expresses S100 protein. Among the cells with neuroectodermal origin, ganglioglioma [6]. S100 is expressed in glia, ependymal cells, Schwann cells and in mel- In our case, no features compatible with atypia was detected, such anocytes [8]. Additionally, it is expressed in Langerhans cells and in as hypercellularity, micronecrosis/geographical necrosis, sheeting, dendritic cells of the lymph nodes in immune tissues. In nervous system; small cells and prominent nucleoli. Mitotic index was less than 4%/ astrocytomas, ependymomas, chordomas and schwannomas express HPF. Similarly, Pope et al. did not find any atypia, necrosis, prominent S100 protein. [8] In our sample, S100 was intensely positive in the nucleoli or other hallmarks of malignancy in their WSMs [12]. Kim meningothelial area surrounding collagen rich whorls. Haberler et al. et al. also declared that none of their WSMs demonstrated mitosis, demonstrated S100 expression in both of their cases [4]. Kim et al. pleomorphism, increased cellularity, or necrosis, even in two cases with found that the spindle cells in sclerotic areas of tumors were steadily extensive brain invasion [8]. Im et al. also observed that signs of sus- negative for S100, but the meningiothelial cells in 4 cases exerted S100 picious anaplasia was absent in their specimens, including high mitotic reactivity [8]. In opposite, Im et al. declared that in all cases tumor cells rate and necrosis [6]. Fukushima et al. also observed neither mitotic were nonreactive for S100 [6]. In our case, meningothelial and spindle figures nor necrosis [3]. There exist no sharp limits, but average values cells encasing acellular sclerosing whorls were strongly im- of Ki-67 indices between different grades of meningiomas. According to munoreactive for S100 compatible with the typical immunoprofile of Maier et al., average Ki-67 values were 3.8%, 7.2% and 15.7% for ty- fibrous meningioma. pical WHO Grade-I, Grade-II and Grade-III, respectively [14]. It shall be also underlined that these values may overlap and a typical me- 5. Pancytokeratin ningioma may have a high Ki-67 index. Kim et al. found that the Ki-67 labelling index was uniformly low in all of their WSM cases (less than Cytokeratins are intermediate filaments of epithelial cells. 0.1%)[8]. Im et al. found that the Ki-67 values of WSMs ranged from Pancytokeratin is an antibody cocktail staining cytokeratins 5, 6, 8, 17 0% to 4% [6]. Fukushima et al. found a Ki67 index of 2.4% [3]. Perven and 18 which are expressed in simple and squamous epithelial cells. In et al. showed almost no proliferating cells with Ki-67 staining [11]. particular, the pseudopsammomas (intracytoplasmic hyaline inclu- Conclusively, it can be commented that WSMs generally have a low sions) in secretory meningiomas are positive for pancytokeratin and proliferating fraction. CEA [14]. In our samples, pancytokeratin (5/6/8/18) was intensely It should be emphasized that each biomarker used in diagnosis of (positive) in the periphery of sclerosing nodules. In contrast, Haberler this rare tumor needs particular interpretations individually. Therefore, et al. did not find pancytokeratin positivity in both of their cases (BMA, they are discussed as distinctive subheadings below and compared with LU5 immunogen: pancytokerain acidic and basic, type I and type II findings of relevant cases in literature (Table 1). cytokines, Mouse anti-vertebrate) [4]. However, with another antibody (BD, CAM 5.2 which bind to cytokeratin 8 and 10 and to a lesser extent 2. Epithelial membrane antigen (EMA) 7 but not to cytokeratin 18–19), they found no staining in one case but moderate staining in the other one [4]. Perven et al. mentioned that EMA is an episialin which localizes at the membrane of milk fat- rare collections of cells were immunopositive for cytokeratin [11]. releasing globular cell membranes, which is expressed at the cell membrane in benign and inside the cytoplasm in the malignant cells. 6. P53 protein EMA immunoreactivity is more frequenty observed in meningothelial or transitional meningiomas than in other subtypes, but nearly 100% of Tumor suppressor gene product, p53 is a nuclear phosphoprotein meningiomas show focal EMA positivity [8]. In our sample, EMA was with a molecular mass of 53 kDa [8]. Wild-type p53 protein is present highly positive. Haberler et al. observed focal single EMA-stainings in in normal cells; but due to its very short half-life, p53 is present in too both of their cases [4]. Pope et al. witnessed diffuse cytoplasmic EMA- few amounts in cells, generally below the detection level of im- reactivity [12]. Kim et al. found that the spindle cells in the sclerotic munohistochemical methods. [8]. Somatic p53 mutations are common areas were consistently negative for EMA, whereas meningothelial cells events in the development of human tumors. Because mutant p53 in 4 of the 5 cases showed membranous staining for EMA [8] . Im et al. proteins often are generally more stable than the wild-type p53 protein, and Fukushima et al. mentioned that tumor cells exhibited positive mutant p53 proteins accumulate and became detectable with IHC [8]. immunoreactivity for EMA in all of their WSM cases [3,6]. On the other Wild-type p53 protein functions as a transcription factor, i.e. as a hand, Perven et al. found that the sparse cells in their one case were modulator which can turn genes either on or off. P53 is a genomic immunonegative for EMA [11]. gatekeeper, it arrests cell cycle and triggers DNA repair following a DNA-damaging insult; however, when the DNA damage is irrepairable, 3. Vimentin it triggers apoptotic cell death [9,13]. In our sample, p53 was highly positive with an antibody which reacts both with the mutant as well as In our WSM sample, mesenchymal marker vimentin was intensely the wild type form of p53. Its epitope maps within the N-terminus (aa positive in the meningothelial areas and moderately positive in the 37–45) of p53. In their study, Kim et al. did not find expression of p53 sclerosing whorls within the tumor. Davidson et al. also found that (DAKO, clone not declared) in any of their cases [8]. Again, Im et al. vimentin was positive in all of their cases [2]. Hope et al. mentioned mentioned that in all of their cases, tumor cells were negative for p53 that in their one WSM case, celullar cytoplasms were stained positive (Dako, 1:300, clone not declared, but DAKO sells DO-7 and 318-6-11

89 İ . Elmaci et al. Clinical Neurology and Neurosurgery 162 (2017) 85–90 clones. Synthetic peptide from the region of human p53 containing References amino acids 49–68 was used for the 318-6-11 clone which stains healthy tissues more than DO-7) [6]. It is likely that in their samples, [1] A. Brandis, S. Mirzai, M. Tatagiba, G.F. Walter, M. Samii, H. Ostertag, p53 was not mutated. Albeit rare as in our case, p53 expressing cells in Immunohistochemical detection of female sex hormone receptors in meningiomas: correlation with clinical and histological features, Neurosurgery 33 (1993) periphery of sclerosing whorls might be a harbinger of an insidious 212–217. clinical course that needs further clarification. On the other hand, we [2] G.S. Davidson, J.K. Hope, Meningeal tumors of childhood, Cancer 63 (1989) think that this possibility is not high due to lack of additional malig- 1205–1210. [3] S. Fukushima, Y. Narita, M. Yonezawa, M. Ohno, H. Arita, Y. Miyakita, K. Ichimura, nancy features and due to positivity of the progesterone receptor, which A. Yoshida, S. Shibui, Short communication: sclerosing meningioma in the deep will be outlined below. sylvian fissure, Brain Tumor Pathol. 31 (2014) 289–292. [4] C. Haberler, C. Jarius, S. Lang, K. Rössler, A. Gruber, J.A. Hainfellner, H. Budka, 7. CD34 Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma, Neuropathol. Appl. Neurobiol. 28 (2002) 42–47. In our case, CD34-staining was highly positive. This antibody reacts [5] J.K. Hope, D.A. Armstrong, P.S. Babyn, R.R. Humphreys, D.C. Harwood-Nash, with a 110 kD glycoprotein, present on the surface of hematopoietic, S.H. Chuang, P.V. Marks, Primary meningeal tumors in children: correlation of clinical and CT findings with histologic type and prognosis, AJNR 13 (1992) myeloid and endothelial cells. Haberler et al. found expression of CD34 1353–1364. in one case, but not in the second case (Novocastra, QBEnd 10, im- [6] A.K. Jaiswal, A. Mehrotra, B. Kumar, S. Jaiswal, M. Vij, S. Behari, L. Pal, fi munogen: Detergent solubilized vesicular suspension prepared from a Lipomatous meningioma: a study of ve cases with brief review of literature, Neurol. India 59 (2011) 87–91. perfusate of human term placenta) [4]. On the other hand, Kim et al. [7] N.R. Kim, S.H. Im, C.K. Chung, Y.L. Suh, G. Choe, J.G. Chi, Sclerosing meningioma: did nod find expression of CD34 (QBEnd 10, DAKO, 1:200 dilution) [8]. immunohistochemical analysis of five cases, Neuropathol. Appl. Neurobiol. 30 (2004) 126–135. [8] S.H. Im, C.K. Chung, B.K. Cho, M.K. Kim, J.G. Chi, Sclerosing meningioma: clin- 8. Progesterone receptor icopathological study of four cases, J. Neurooncol. 68 (2) (2004) 169–175. [9] A.J. Levine, p53, the cellular gatekeeper for growth and division, Cell 88 (1997) In our case, progesterone receptor (PR) was intensely positive in the 323–331. fi [10] A. Perry, S.L. Stafford, B.W. Scheithauer, V.J. Suman, C.M. Lohse, Meningioma periphery of aggregated nodules and scarcely positive in uncalci ed grading: an analysis of histologic parameters, Am. J. Surg. Pathol. 21 (1997) whorls with an antibody which recognizes N-terminal region of the A 1455–1465. isoform of the human PR. Haberler et al. did not detect PR expression in [11] G. Perven, P. Entezami, D. Gaudin, A rare case of intramedullary ‘whorling-scler- both of their cases (DAKO, PGR 636 immunogen: Formalin-fixed re- osing' variant meningioma, Springerplus 4 (2015) 318, http://dx.doi.org/10.1186/ s40064-015-1110-8. combinant full-length A-form of human progesterone receptor) [4]. [12] L.Z. Pope, C.E. Tatsui, M.S. Moro, A.C. Neto, L.F. Bleggi-Torres, Meningioma with Similarly, Perven et al. did not detect PR in rare collections of cells extensive noncalcifying collagenous whorls and glial fibrillary acidic protein ex- surrounding a highly hyalinized WSM [11]. pression: new variant of meningioma diagnosed by smear preparation, Diagn. Cytopathol. 28 (2003) 274–277. [13] M. Shi, D. Liu, B. Shen, N. Guo, Helpers of the cellular gatekeeper-miRNAs dance in 9. Conclusion P53 network, Biochim. Biophys. Acta 1805 (2010) 218–225. [14] A. Taraszewska, E. Matyja, Secretory meningiomas: immunohistochemical pattern of lectin and ultrastructure of pseudopsammoma bodies, Folia Neuropathol. 52 The recognition of the WSM subtype is important to avoid an er- (2014) 141–150. roneous diagnosis of malignancy which may cause unnecessary and harmful application of chemotherapy and radiotherapy especially detrimental for the mental development of children [2].