Ossified metaplastic meningiomas: A systematic review on a rare subset of "brain stones".

•Metaplastic meningiomas are rare entities, and intracranial osseous subtype are even more rare.•Gross total resection is considered the best treatment choice.•Differential diagnosis is mandatory, including osteoma, osteoblastoma, and calcified giant aneurysms.•This rare entity must be considered in a global approach and tailored surgical technique.

Introduction

Metaplastic meningiomas are rare entities, arising from the pluripotential arachnoid cap cells that can differentiate in different mesenchymal tissues (Johnson et al., 1989; Alafaci et al., 1999). They are classified as Grade 1 tumors according to the World Health Organization (WHO), with slow growth and prevalent spinal localization. Clinical symptoms are various, mostly depending on size and location (Tai et al., 2010). The authors report a rare case of a female patient that presented a status epilepticus after an abdominal surgery procedure with history of fronto-parietal extra-axial calcified mass. A systematic review of the relevant literature was also performed. The objective of this paper was to clarify the main characteristics of this rare meningioma subtype, focusing on aspects influencing surgical technique, to guide neurosurgeons on global approach of these patients.

Materials and methods

A systematic review of all the previously reported intracranial metaplastic meningiomas was performed according to the PRISMA guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analysis) (Fig. 1).

Fig. 1

PRISMA flow diagram summarizing our searches and selection of studies included in the literature review of ossified metaplastic meningiomas.

Two authors (F.P. and G.S.) independently performed a search on PubMed and Scopus databases from 1989 to March 2022, using the following Mesh terms:

“Metaplastic Meningioma AND brain” (25 results)

“Ossified Meningioma AND brain” (12 results)

“Ossified AND intracranial AND Meningioma” (17 results)

“Metaplastic AND Meningioma” (84 results)

“Osteoblastic AND Meningioma” (44 results)

According to PRISMA guidelines, the research order consisted of screening titles first, then abstracts and full papers (Fig. 1). Finally, the references of the articles included were screened. No automation software was used.

To be included, studies had to analyze a single or group of patients affected by metaplastic meningiomas, osseous subtype, with definitive histopathological analysis. No time limits were set up. Only English articles were selected. The authors aimed to investigate and highlight the current state of art in metaplastic meningiomas treatment, according to their rarity, focusing on indications and outcomes. A database based on the previously selected case reports or case series (11 studies) was created. (Table 1). Data extracted from each study were (1) authors, (2) year of publication, (3) study design, (4) number of patients included, (5) age, (6) sex, (7) symptoms, (8) neurological examination, (9) tumor location, (10) Simpson grade, (11) presence of calcification, (12) presence of psammoma bodies. Descriptive statistical analyses were conducted.

Table 1

Literature review regarding previously published cases of Cranial ossified metaplastic meningiomas. N.R. ​= ​Not Reported; CPA = Cerebellopontine Angle.

N°	Authors/Year	N° of patients	Age (years), Sex	Symptoms	Neurological Examination	Location	Simpson Grade	Calcification	Psammoma Bodies
1	Johnson et al., 1989 (Johnson et al., 1989)	1	53, M	Dizziness, Blurred vision, Headache	Negative	4th ventricle	I	Yes	Yes
2	Alafaci et al., 1999 (Alafaci et al., 1999)	1	28, F	Headache, diplopia	Left lateral emianopsia paralysis of IV and VII left cranial nerves	Right lateral ventricle	I	Yes	Yes
3	Tai et al., 2010 (Tai et al., 2010)	1	60, M	N.R.	Headache, left limbs weakness	Right frontal lobe	I	Yes	No
4	Barresi et al., 2011 (Barresi et al., 2011)	5	37, F	Headache, seizures, subjective vertigo	Negative	Left temporo-basal	I	Yes	Yes
			42, F	Headache, reduction in visual acuity	Papilledema	Left fronto-temporo- parietal convexity	IV	No	No
			62, F	Progressive hyposthenia of right hemisoma	Right brachio-crural hemiparesis	Left frontal convexity	I	Yes	Yes
			57, F	Hyposthenia of left hemisoma, aphasia	Temporo-spatial disorientation, left lateral hemianopia, brachio-crural hemiparesis and left Babinski	Right parieto- occipital convexity	I	Yes	Yes
			55, F	Headache	Negative	Clinoid	I	Yes	Yes
5	Huang and Petersson, 2011 (Huang and Petersson, 2011)	1	26, M	Generalized tonic-clonic seizures	N.R.	Right frontal convexity	N.R.	Yes	No
6	Tang et al., 2013 (Tang et al., 2013)	6	41, M	Headache	N.R.	Right Lateral ventricle	I	Yes	N.R.
			48, F	Blurred vision	N.R.	Petroclival	III	N.R.	N.R.
			60, F	Seizures	N.R.	Right Petroclival	I	N.R.	N.R.
			34, M	Seizures	N.R.	Right Frontal parasagittal	I	N.R.	N.R.
			47, M	None (incidental)	N.R.	Right CPA	I	N.R.	N.R.
			40, M	Seizures	N.R.	Right Sphenoid ridge	II	N.R.	N.R.
7	Caffo et al., 2016 (Caffo et al., 2016)	4	83, F	Headache, neurologic delay	Right hemiparesis, right Babinski sign	Left frontobasal	III	Yes	Yes
			47, F	Headache, visual loss	Papilledema	Left frontotemporal	I	No	Yes
			73, F	Seizures	Negative	Left frontotemporal	I	Yes	Yes
			49, M	Headache	Negative	Sphenoethmoidal plane	I	Yes	Yes
8	Indiran et al., 2017 (Indiran, 2017)	1	33, M	Headache	N.R.	Left frontobasal	N.R.	N.R.	N.R.
9	Choi et al., 2018 (Choi et al., 2018)	1	26, M	Intermittent right upper extremity weakness	right Babinski sign	Left parietal	II	Yes	N.R.
10	Priyadharshini et al., 2020 (Priyadharshini et al., 2020)	1	28, M	Headache	Negative	Left parietoccipital	N.R.	Yes	Yes
11	Kim et al., 2020 (Kim et al., 2020)	4	60, F	Blurred vision	N.R.	Anterior falx	I	Yes	N.R.
			62, M	Headache	N.R.	Midline frontobasal	I	Yes	N.R.
			37, F	Seizures	N.R.	Right frontal convexity	IV	Yes	N.R.
			55, F	Headache	N.R.	Midline falx	IV	Yes	N.R.

Results

A total of 182 studies were identified through the PubMed and Scopus databases, 140 articles after duplicates removal. First, articles were selected by the presence in their title of the words “Osteoblastic” or “metaplastic” or “ossified” (41 articles). Then, the authors rejected studies dealing with spinal meningiomas, or different histopathological subtypes (21 articles). After screening by title, 20 abstracts were screened, according to the selection criteria. Thus, 14 studies by full-text analysis were identified. 1 record was identified through references section screening. Finally, the authors included in the systematic review 11 articles, summarized in Table 1 (Johnson et al., 1989; Alafaci et al., 1999; Tai et al., 2010; Huang and Petersson, 2011; Barresi et al., 2011; Tang et al., 2013; Caffo et al., 2016; Indiran, 2017; Choi et al., 2018; Priyadharshini et al., 2020; Kim et al., 2020).

All the selected records were used to structure a unique database to evaluate surgical outcomes and histopathological features. Patients included were 26, 11 males, 14 females (1 not reported). The mean age was 47,81 ​± ​14,78 years (range 26–83). Symptoms and location were heterogenous, not different from common meningiomas subtypes. 15 patients achieved a Simpson grade I after surgery (57.69%). 20 tumors had calcifications (76.92%), and 10 lesions (38.46%) formed psammoma bodies.

Case description

A 71-year-old female patient was admitted to our emergency department because she presented a status epilepticus with right hemisome motor seizures. The patient performed an anterior pelvectomy for a bladder cancer few days prior to symptoms presentation. She had a history of a calcified left fronto-parietal extra-cerebral lesion, unmodified during previous follow-ups.

Neurologic examination showed right brachio-crural weakness (BMRC 3/5), right hemisome brisk reflexes, right hemisome hypoesthesia.

She performed a brain MRI that documented a left fronto-parietal extra-cerebral lesion with 40 ​× ​35 ​mm in axial diameters, with ring peripheral enhancement on Gd-T1WI (Fig. 2) and focal left frontal anterior hyperintensity on FLAIR sequences. A brain CT scan was also performed, showing a completely calcified lesion (Fig. 2).

Fig. 2

Pre-operative brain CT (A) and MR (B) scans.

She was planned for operative management. Under general anesthesia, in supine position with head fixed in Mayfield holder. The patient underwent left fronto-parietal craniotomy. Dura mater appeared thickened, calcified, and was removed with a circumferential durotomy. Intra-operatively, she had a hard calcified nodule of 3.5 ​× ​3 ​× ​2 ​cm extra-axially over the left fronto-parietal region, compressing motor area. The lesion was firmly attached to the dura mater; a gently arachnoid dissection with cottonoids was performed, and the lesion was removed en-bloc (Fig. 3).

Fig. 3

En-bloc removal of the totally calcified lesion. (A) Brain side. (B) Dural side.

Intraoperative neurophysiological monitoring showed mild MEPs improvements at the end of surgical procedure. Histologic samples documented a metaplastic ossified meningioma, with psammoma bodies (WHO grade 1). Post-operatively, the patient showed a complete subsidence of seizures, and a partial regression of the motor deficits (BMRC 4/5). During post-operative period, she performed a contrast-enhanced brain MRI, that documented a complete meningioma removal (Fig. 4).

Fig. 4

Post-operative brain MR scan demonstrating the complete removal of the calcified mass.

Discussion

Metaplastic meningiomas are slow-growing tumors, classified as Grade 1 according to WHO classification. The originating arachnoid cell passes through a mesenchymal differentiation into osseous, cartilagineous, smooth muscle, xantomatous of lipomatous tissues, alone or in combination (Alafaci et al., 1999; Tai et al., 2010). These represent 4 different entities of the same subtype. As we know, 26 cases of intracranial ossified metaplastic meningiomas have been previously reported in literature (Table 1).

The diagnosis is not different from the other meningiomas subtypes (Johnson et al., 1989; Barresi et al., 2011; Caffo et al., 2016; Indiran, 2017; Choi et al., 2018; Priyadharshini et al., 2020; Kim et al., 2020). In fact, the most common presenting symptoms are headache (12/26) and seizures (6/26). Neurological examination of patients affected is strictly related to the tumor location. The most frequent locations were convexity (9/26) and skull base (7/26). Brain CT scan examination is mandatory, because the features of ossified meningiomas in MRI is not typical (Huang and Petersson, 2011). This tumor subtype is mainly a slow-growing lesion, with low mitotic index, even if a residual portion is left in situ (Tai et al., 2010). Gross total resection (GTR) is considered the best treatment choice (Alafaci et al., 1999). In case of a “hard rock” appearance of this meningioma subtype, a Simpson Grade I is often challenging, especially in skull base lesions (Alafaci et al., 1999). As regard superficial lesions in non-eloquent areas, the attempt to gain GTR is often performed by using en bloc resection, after gentle arachnoid dissection. In cases of location in eloquent regions, or involvement of nerves or great vessels, a piecemeal resection using high-speed drill, Kerrison rongeurs and pounches is the best surgical approach (Alafaci et al., 1999). Often, leaving a residual fragment is the only chance, as seen in 7 patients of the present review. Considering the case series by Tang et al., during a 2-year follow-up, a low rate of recurrence was documented (only 2 cases) (Tang et al., 2013).

The presence of calcification is often matched by the presence of psammoma bodies. Nonetheless, Huang et al. reported a rare case of ossified metaplastic meningioma with several calcified areas and wire-like streaks of calcification, forming patterns reminiscent of chicken wires (Huang and Petersson, 2011). Considering their rarity, differential diagnosis is mandatory, including osteoma, osteoblastoma, fibroma, even calcified giant aneurysms (Alafaci et al., 1999).

Study limitations

The present review has several limitations. First, papers included in systematic review are case reports or case series, and the level of evidence is scant. Moreover, general approach to the patient, surgical techniques, complications rate, long term outcome, are features not globally highlighted in the previous literature.

Conclusion

Metaplastic meningiomas are rare entities, classified as Grade I according to WHO. Their existence must be considered because of their unicity in a multimodal approach and tailored surgical technique.

Ethics approval

There is no ethical issue in this paper.

Funding support and sponsorship

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Patient consent

Patient gave her consent for images or other clinical information reported in the paper.

Declaration of competing interest

There are no conflicts of interest.