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Abstract
Background: Meningiomas are generally slow-growing, benign, and non-infiltrating in nature. They are usually easy to diagnose cytologically if they are of the meningothelial type; however, they may cause diagnostic challenges when they manifest as unusual morphological variants, like the microcystic type. Because of the rarity of microcystic meningioma (MM), information on its cytological features is rarely available in the literature. Objectives: The goal of this study is to review the cytological features of MM in crush preparations prepared at the time of intra-op consultation and to identify the more common features which are helpful in rendering a correct diagnosis. Material and Methods: Cytological features of five cases of MM were reviewed and noted from the records. Results: There were five patients of MM with a male: female ratio of 1.5:1 and a mean age of 52 years. All tumors were supratentorial and dura-based. Magnetic resonance imaging (MRI) showed low signal intensity on T1 and high signal intensity on T2 weighted images in four cases. Cytosmears were moderate-to-highly cellular. There were variable-sized cystic spaces within the meningothelial cell clusters. In four cases, nuclear pleomorphism was frequently observed. Nuclear pseudoinclusions, atypical mitoses, vascular proliferation, and necrosis were absent in all cases. Whorling and psammoma bodies were seen in only one case. Conclusion: Cytological features identified would be helpful in the diagnosis of microcystic meningiomas, especially in unusual radiological findings. Their unusual cytological features might lead to problems in differential diagnosis from other intracranial tumors, including glioblastoma, metastatic tumor, etc.
Keywords: Meningioma, microcystic, smear, squash
How to cite this article: Introduction 
Smear cytology has become increasingly popular in the past few decades as an alternative to frozen sections for central nervous system tumors. The main advantages of smear cytology for intraoperative diagnosis are quick results, ease of preparation, technical simplicity, preserved cytological features, and the requirement of a small sample size.
Microcytic meningiomas (MMs) are known to be unusual morphological variations of meningiomas in which microcysts are present throughout the tumor. Although the clinico-histopathological features of this entity are well known, the cyto-morphological features of these have rarely been demonstrated, and in the absence of knowledge of cytological presentation, one may misdiagnose the benign tumor as malignant. This study is an attempt to identify the more common cytological features of MM on squash smears that may help in rendering a correct intraoperative diagnosis.
Material and Methods Five histologically diagnosed cases of MM and records of these cases were retrieved from archives of the pathology department and medical record department of our hospital. In all cases, the tumor samples were obtained during surgical resection. Crush smears were prepared by taking a small bit of tissue from the specimen and gently crushing it between two glass slides. The smears were then stained by the hematoxylin and eosin (H&E) method and Giemsa stain. We reviewed crush cytology smears and routine paraffin sections along with immunohistochemical (IHC) markers of all cases. The demographic profile and radiological findings were also noted from the records. The study was approved by the Institutional ethics committee, BMHRC on 25/04/2019.
Results There were five patients with MM out of which three were male and two were female patients (M: F ratio: 1.5:1). The age ranges between 40 and 75 years (mean: 52 years) [Table 1]. All tumors were supratentorial and dura-based. MRI showed low signal intensity on T1 and high signal intensity on T2 weighted images [Figure 1] except in one case which had both T1 and T2 hyperintense with moderate perilesional edema.
Figure 1: MRI images (a). High signal intensity on T2-weighted image, (b). Low signal intensity on T1-weighted image, (c). High signal intensity on post-contrast image
Table 1: Showing clinicoradiological and squash smear findings of cases of MMCytological findings on squash smear preparation are as follows:
All tumors were soft enough to be smeared satisfactorily [Figure 2]a. Smears were moderate-to-highly cellular and showed medium-to-large-sized, cohesive clusters and sheets of uniform singly scattered meningothelial cells. The most significant feature is variable-sized cystic spaces [Figure 2]b within the cell clusters. Most of the cells have abundant light lacy eosinophilic cytoplasm with an indistinct cell border. Nuclei are round to oval with fine evenly distributed nuclear chromatin and inconspicuous nucleoli. In four cases, atypical-looking cells were frequently noted [Figure 2]c. The cells show mild to moderate nuclear pleomorphism and mild hyperchromasia. Whorling and psammoma bodies were seen in only one case. Nuclear pseudoinclusions, atypical mitoses, vascular proliferation, and necrosis were absent in all cases. In three cases, the correct diagnosis was delivered, whereas in two cases, the possibility of a high-grade tumor was given.
Figure 2: (a): Squash smear showing moderate cellularity. Inset: glass slide showing the spread of tumor tissue. (b): cohesive clusters and sheets of meningothelial cells with variable-sized cystic spaces. (c): 40 × cells with atypical large nuclei. (d): 40 × Histologically, sieve-like spaces. (e): atypical cells. (f): EMA-positive tumor cellsHistologically, these tumors were composed predominantly of stellate and spindle cells with long, thin interconnecting cytoplasmic processes arranged in a complex network. The resulting cellular architecture was "sieve-like" [Figure 2]d in appearance because of the formation of numerous small "cyst-like" spaces interposed between the cytoplasmic processes of the tumor cells. Atypical cells with large irregular nuclei were noted [Figure 2]e. All tumors were reticulin-poor. Marked vascular proliferation was noted throughout the tumor in four cases. The meningothelial cells showed immunoreactivity for EMA and vimentin [Figure 2]f. The Ki-67 index was 5–7% in two cases, whereas in the rest, it was less than 2%. All tumors were resected, and none of these recurred during a follow-up period ranging from 3 to 8 years.
Discussion Squash cytology for the intra-op diagnosis of CNS lesions has been utilized for about 50 years. Although the frozen section has the advantage of better architectural preservation, squash/scrape cytology often yields superior cytological detail of cells and is devoid of freezing artifacts which is commonly seen in cases where there is interstitial edema. There are only few studies conducted on the squash cytology of MM.
Meningioma shows various histomorphological variants. MMs are rare subtypes, accounting for 1.6%[1] of all intracranial meningiomas, and have unusual morphological variation. These tumors were originally described by Masson who labeled them "humid" or vacuolated meningiomas because of their gross appearance.[2] The term "microcystic" was suggested by Kleinman et al.[3] in 1980. The WHO categorized this variant as a grade I tumor[4] Clinically, these tumors are slow-growing and produce neurological signs and symptoms due to the compression of adjacent structures. The pathogenesis of these tumors is unclear, although transudation of low protein-containing fluids was previously suggested.[2] The age of affected patients ranges between 3 years and 74 years, with slightly more female predominance. Most lesions manifest in the cerebral convexities or parasagittal region.[3],[5] Similar findings were seen in our study with slight male preponderance, an average age of 52 years, and attachment with dura mater. Radiologically, in various studies, it is depicted that the MRI features of MM differ from that of more common variants of meningioma. Kubota et al.[6] reported a single case of MM in which they found that on MRI, T1 weighted images were hypointense and remained hypointense even after intravenous administration of Gd-DTPA. In another study carried out by Kim HS et al.[7] on 11 cases of MM, MRI findings show low signal intensity on T1, high signal intensity on T2 weighted images, and peripheral rim enhancement with a dural tail sign, and all cases showed moderate-to-severe degrees of peritumoral edema. In this series, in four cases, we found similar findings, and in one case (known case of treated carcinoma breast), the tumor was both T1 and T2 hyperintense and had moderate perilesional edema. Usually, the combination of characteristic appearances of conventional meningioma on imaging and the appearance during operation means that the surgeon is rarely in doubt that a tumor is a meningioma, but pre-operative findings of this variant were different from conventional types and the things would become worse when the patient had some previous history of the tumor as this may bias the surgeon.
Meningiomas are common benign tumors accounting for 13% to 26% of intracranial neoplasms.[4],[8] Conventional meningiomas are rubbery, firm, and well-demarcated tumors that have a dural attachment. Intraoperative crush cytology of these is usually easy to recognize. In most of the cases, low-power magnification demonstrates generally cohesive syncytial clusters of meningothelial cells with irregular margins and is unrelated to blood vessels unlike those of astrocytic tumors. The nuclei are oval in shape with diffuse chromatin and indistinct or small nucleoli. The cytoplasm is indistinct, and often intranuclear pseudoinclusions are identifiable. Psammoma bodies if present are diagnostically useful. Nuclear pleomorphism is rare. Whorl formation is variable but almost always seen. Single intact meningothelial cells are seen in the background and consist of eccentrically placed bland nuclei with abundant "tissue paper" or delicate, wispy-appearing cytoplasm. In the secretory variant of meningioma, sometimes, bright eosinophilic pseudopsammoma bodies are seen.
MM is characterized by cells with thin, elongated processes encompassing microcysts and creating a cobweb-like background.[4] The cytoplasm of the tumor cells is more abundant than that of classic meningioma and has a faintly eosinophilic or cyanophilic vacuolated appearance. Siddiqui et al.[9] suggested that the cytological findings may not reflect the histological subtype. However, Fukuoka et al.[10] stressed that abundant and vacuolated cytoplasm and cystic spaces of various sizes, as well as rare nuclear inclusions or grooves, may be distinguishing findings in MM. The lack of intranuclear inclusions and psammoma bodies in this variant has been reported in some reports.[9],[10] In this study, we also found similar findings like numerous cystic spaces within the cell clusters and cells with abundant light lacy eosinophilic cytoplasm with indistinct cell borders. Nuclei are round to oval with fine evenly distributed nuclear chromatin and inconspicuous nucleoli. In four cases, the presence of nuclear pleomorphism was evident in varying degrees. Whorling and psammoma bodies were seen in only one case. Nuclear pseudoinclusions, atypical mitoses, vascular proliferation, and necrosis were absent in all cases. In one case, nuclear pleomorphism was extensive. The patient was a known case of treated invasive ductal carcinoma. Post-5-year disease-free period, she presented with dura-based mass. The radiological features were different from the conventional meningiomas. Intraoperatively, the tumor was soft. With all these details and marked nuclear pleomorphism, absent whorls and sheets, a diagnosis of high-grade tumor was given on squash smear examination; however, after routine processing, it was diagnosed as MM. Such cases may pose difficulties in the correct diagnosis.
MM may be confused with tumors that may have dural attachment. The differentials of MM are (i) angiomatous meningioma which has abundant blood vessels with marked hyalinization, (ii) hemangioblastoma which shows numerous delicate capillaries and foam cells, (iii) pilocytic astrocytoma which has a prominent microcystic component and usually has mild cellularity, and (iv) metastatic tumors which may mimic meningioma radiologically and sometimes have a dural attachment as well. These have mitotic figures and acinar, glandular, or papillary fronds. In some cases where there is absent epithelial cohesiveness, background necrosis or mucin can be identified, and (v) glioblastoma may sometimes be a differential to MM, especially when they are infiltrating leptomeninges. (vi) Hemangiopericytoma is also one of the differentials as it has no cell lobules, whorls, and psammoma bodies. They are well circumscribed and have a meningeal attachment; however, they are more cellular and have increased vascularity and prominent nucleoli. Mitotic activity is sometimes present. The presence or absence of a dural attachment and clinical history of any primary tumor are some of the helpful pointers toward correct diagnosis. Grossly micro- or macrocysts are sometimes evident and, on histology, this variant of meningioma is characterized by cells with thin, elongated processes encompassing microcysts and creating a cobweb-like background.
Immunohistochemistry of MM showed immunoreactivity for vimentin, and EMA was negative for S-100, NSE, GFAP, Pan-CK, CD-34, and CEA. Histomorphological and IHC findings are similar in our cases as well. In this study, we found that the MM has a different intraoperative presentation, and also, the smearing pattern and its cytological picture are different from conventional meningioma. Because these are rare tumors, one may misdiagnose if not aware of the features or has less information on radiological features or may get biased with the clinical findings. Care must be taken while seeing these tumors.
Conclusion Squash smears can be utilized for diagnosing MM. This entity is prone to misdiagnosis because of its unusual imaging features, uniformly spread smears, microcystic spaces, bizarre/pleomorphic tumor cells, and absence of whorling, psammoma bodies, and nuclear pseudoinclusions. To avoid misinterpretation we must carefully look for the absence of high cellularity, atypical mitoses, vascular proliferation, and necrosis. The assessment of the squash smears not only relies on cytological details but also a subjective appraisal of the clinical and radiological details in each case.
Acknowledgement
The authors are thankful to the histopathology and cytology technical staff.
Financial support and sponsorship
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Conflicts of interest
There are no conflicts of interest.
References 
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/joc.joc_28_22
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