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Neuropathology 2015; 35, 137–147

doi:10.1111/neup.12174

O rig i na l Ar t i cl e

Chordoid meningiomas: Incidence and clinicopathological features of a case series over 18 years Antonio Di Ieva,1* Simin Laiq,2* Romina Nejad,1 Erika M. Schmitz,1 Hussein Fathalla,1 Jason Karamchandani,2 David G. Munoz2 and Michael D. Cusimano1 1

Department of Surgery, Division of Neurosurgery, 2Department of Laboratory Medicine and Pathology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

Chordoid meningioma (CM) is a rare subtype of meningioma, classified as grade II, which exhibits a high rate of recurrence following subtotal resection. We retrospectively examined nine cases of chordoid meningioma over a case series of 1743 meningiomas (0.52%) operated upon at our institution from 1995 to 2013. All the reported clinicopathological findings were analyzed. Two hundred and twenty-one CM cases have been published to date worldwide and few single-center large case series have been issued. Seventy-five percent of the cases that underwent subtotal resection at our institution had recurrence within 1 year. Total resection of the tumor should be the major objective of surgery to reduce the possibility of tumor recurrence. The percentage of chordoid features within the tumor specimen could assist in predicting the pathogenesis of the lesion. The correlation of the index of proliferation to recurrence rate is still controversial. Much debate exists with regard to the role of adjuvant radiotherapy in CM cases. Immunohistochemical, cytological and ultrastructural studies should be used in combination to assure a correct diagnosis of CM. Owing to the rare occurrence of this meningioma subtype, larger case series are required to assist in providing a reference for diagnosis and to improve the therapeutic management of CM. Key words: atypical meningioma, brain tumor, chordoid meningioma, intracranial meningioma, meningioma recurrence.

Correspondence: Antonio Di Ieva, MD, PhD, Division of Neurosurgery, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8. Email: [email protected] *These authors contributed equally. Received 25 May 2014; revised 14 September 2014 and accepted 15 September 2014; published online 6 November 2014.

© 2014 Japanese Society of Neuropathology

INTRODUCTION Chordoid meningioma (CM) is a rare subtype of meningioma. While meningiomas account for about 24–30% of all primary intracranial tumors,1 this particular variant accounts for less than 1.0% of all intracranial meningiomas.2,3 The primary histologic features of the lesion include “epithelioid cells, often partly vacuolated, within a pale basophilic, myxoid matrix” with lymphoplasmacellular infiltrates.2 Although “myxoid” and “vacuolated” were employed as descriptive terms in the past,4,5 Kepes et al.6 first devised the term “chordoid” in their report of seven chordoid meningioma cases. Chordoid meningiomas seem to have a more aggressive nature, a high propensity to recur, and are classified as grade II in the World Health Organization (WHO) classification system (ICD-O code: 9538/1).7 Two hundred and twenty-one cases of chordoid meningioma have been published to date worldwide. Few singlecenter large case series have been issued.2,8–10 Despite its slow-growing prevalence in the medical literature, knowledge regarding the clinical presentation and commonalities of pathologic findings is limited, and there is no standardized method for reporting data. Owing to the rare occurrence of this meningioma subtype, here we retrospectively review the cases of chordoid meningiomas of our institution and review all published cases. We review the role of patient demographics (age and gender), tumor characteristics (resected tumor size, localization, biological characteristics, percentage of chordoid features, MIB-1/Ki-67 staining, genetic changes and molecular biomarkers, infiltration of lymphocytes), systemic correlations, management by adjuvant radiotherapy, and differential diagnosis according to immunohistochemistry, cytology, histology and ultrastructural features. The authors aim to advance medical knowledge regarding chordoid meningioma to

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assist neurosurgeons, neuropathologists and clinicians in tertiary care settings, while emphasizing the need for standardization of data reporting.

METHODS Data collection Sixteen patient cases displaying chordoid patterns from 1995 to 2013 were identified by the Department of Laboratory Medicine and Pathology at the St. Michael’s Hospital, Toronto, Ontario, Canada. Only patients with primary lesions were considered. Clinical charts were obtained from the hospital database. Patient data, clinical findings, radiological reports and operative reports were collected. Pathological reports were reviewed for microscopic and macroscopic descriptions, immunohistochemical findings and pathological diagnosis. The primary tumor specimens as well as the specimens of recurrence cases were collected and reviewed by three neuropathologists (SL, JK, DM) for identification of variables of interest and for diagnosis verification. The review diagnosis was inconsistent with CM for five cases and two cases were not part of the series of the single institution: a total of seven cases were removed from the study. Nine cases of chordoid meningioma were included. The hospital’s Research and Ethics Board approved this retrospective study.

Literature review The Hospital Library and University database searches were performed to identify all case series and case reports of patients with chordoid meningioma. PubMed (1950 to May 2014), MEDLINE (1946 to May 2014) and Google Scholar were searched using key words including Chordoid Meningioma, Chordoid, Atypical Meningioma, Chordoid Brain Tumor, Outcome of Chordoid Meningioma, WHO Grade II Meningioma and Histopathology of Chordoid Meningioma. This was followed by manual searches through the reference lists of all articles. Only articles in the English language were included.

Histological and immunohistochemical aspects The Department of Neuropathology collected the tumor specimens during and after surgery as per normal standard of care and hospital protocol. Tumors were promptly fixed with formaldehyde, paraffin wax-embedded and processed for pathological diagnosis. The lesions were sectioned at 4 microns, and routinely stained with HE or hematoxylin-phoxyn-saffron (HPS) and some with Alcian Blue. The cases were selected on the basis of having characteristic chordoid morphologic features, which included

cells arranged in cords or trabeculae in an abundant mucoid background. Immunohistochemical staining was performed using monoclonal antibodies directed against progesterone receptors and Ki-67 (MIB-1 antibody) and retrospectively reviewed. The MIB-1 labeling index (MIB-1 LI), a marker of cell proliferation, was calculated over the total. The neuropathologists examined all tumor cross-sections and agreed on areas of most dense cell proliferation, denoted as the “hot spot” method. Images were captured at 100× for analysis using ImageJ (US National Institutes of Health, Bethesda, Maryland, USA, http://imagej.nih.gov/ij/) with the “Immunoratio” Plugin. The automated algorithm subsequently calculated the MIB percentage. A visual inspection of all slides and average of chordoid percentage was calculated for each case.

RESULTS Clinical features Patient demographics are summarized in Table 1. We identified nine patients who underwent surgery for resection of chordoid meningioma at our institution from 1995 to 2013. This accounts for 0.52% (9/1743) of all patients diagnosed with meningioma at our institution during that time period. Of the nine cases, there were three men and six women with an age range of 19–85 years (mean: 60 years). All tumors were located in the supratentorial region. Anatomical localization of the tumors varied, with the frontal region being the most common location (n = 3). Other localizations were the frontotemporal (n = 1), parietal (n = 1), middle fossa (n = 1), posterior left optic canal (n = 1), parasagittal and falcine (n = 1), and frontoparietal (n = 1) regions. MRI was available in four cases, while CT scan was available in all cases. Perilesional edema was observed in seven cases, three cases exhibited midline shift and local moderate to severe mass effect was seen in seven patients. Most of the lesions exhibited homogeneous enhancement (n = 4), while others exhibited mixed or minimally heterogeneous enhancement (n = 3). A clear dural tail was visible in three cases and bone invasion was noted in two cases. Extension of tumor resection and Simpson Grade11 of meningioma resection are reported in Table 1. Gross-total resection (GTR) was achieved for five primary lesions, three primary lesions were sub-totally resected and extent of resection was not available for the last case. Three out of the four (75%) cases that underwent subtotal resection (STR) for their primary tumor had a recurrence (cases 4, 6 and 8). Two of these recurrences were residual regrowth (cases 6, 8) and one recurred in a new location (case 4). © 2014 Japanese Society of Neuropathology

© 2014 Japanese Society of Neuropathology 4 × 2.6 × 3

3 × 4.5 × 4

4.14.5 × 3.4

4×3×3

4.3 × 2.8 × 3

8.8 × 4.7 × 4.4

1 × 0.9 × 1.4

3 × 2.7 × 2.9

4×3×5

3×4×4

5×4×4

6×5×5

Tumor size (cm)

Headache, seizure, cognitive decline Unilateralweakness, apraxia, headache, nausea, vomiting No symptoms. Detected on repeat MRI Unilateral weakness, sloppy gait

Dysphasia, mild unilateral facial asymmetry and numbness Dysmetria, unilateral dysdiadochokinesia, leg drag and hand agraphesthesia Bifrontal headache, unilateral focal seizure with secondary generalization Headache, eye dryness, gait and balance problems Facial numbness, diplopia, unilateral eye pain, proptosis and papilledema Unilateral, visual loss, near blindness. L optic neuritis Headache, seizures, unilateral side weakness and inferior quadrantanopsia, word finding difficulties, clumsiness of gait and hand function Headache, unilateral inferior quadrant anopsia and dysphasic.

Signs and symptoms

GTR/1

STR/2

N/A

GTR/1

GTR/2

STR/4

STR/3

GTR/1

STR/3

GTR/1

GTR/1

GTR/1

Extent of resection/ Simpson grade

No

Yes

N/A

N/A

Yes

N/A

N/A

Yes

No

No

No

No

Radiotherapy (Yes/No)

No

No

Yes

No

No

Yes

N/A

No

Yes

No

No

No

Recurrence (Yes/No)

–

–

12 mo

–

–

12 months

–

–

8 months

–

–

–

Time to recurrence

AW (2 months)

AW (2 months)

–

AW (69 months)

AW (60 months)

–

AW (60 months)

AW (36 months)

C

AW (120 months)

AW (12 months)

DDC

Outcome (months from surgery to last follow-up)

AW, alive and well; C, complication; DDC, death due to complication; GTR, gross total resection; L/R, left/right; N/A, not available; Post./Ant., posterior/anterior; Rn, recurrence; STR, subtotal resection; U, unilateral.

Frontoparietal, parasagittal

M/73

9

Frontal

Frontal

M/49

8

Parasagittal and falcineAnt. parietal Frontal

8R1

F/76

7

6R1

M/41

6

Parasagittal and falcine – Ant. parietal

Optic canal

F/19

F/64

4

Midline bifrontal and corpus callosum Middle cranial fossa

5

F/49

3

Parietal

Sphenoid Wing

F/85

2

Frontotemporal

Location of tumor

4R1

F/84

Gender (M/F)/age (years)

1

Case number

Table 1 Patient demographics and clinical profile characteristics of study group

Chordoid meningioma 139

140 Tumor recurrences occurred between 8 to 12 months duration after the primary surgery for all recurrent cases. GTR was achieved for the recurring lesion in two cases (cases 4, 6) and STR in one case (case 8). All three cases underwent adjuvant radiotherapy. A third recurrence was suspected in case 6; however, investigation showed radiation-induced necrosis in the left frontoparietal region of the brain. Tumor transformation occurred to a higher grade on recurrence (case 4), namely a WHO grade III anaplastic meningioma, and was consequently excluded from Table 1. None of the cases were associated with Castleman’s disease. No deaths correlating to the CM diagnosis were recorded; however, one patient died due to post-operative stroke.

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Histological and immunohistochemical results Histological and immunohistochemical results are presented in Figure 1. The primary tumor specimens were reviewed for prominence of nucleoli (n = 6/9, seen in the chordoid meningioma areas, as well as the areas showing atypical meningioma morphology), small cell change (n = 3/9, seen in areas showing atypical meningioma morphology), presence of cellular atypia (n = 6/9, seen in the chordoid meningioma areas, as well as the areas showing atypical meningioma morphology), nodules of high cell density (n = 4/9, seen in the chordoid meningioma areas, as well as the areas showing atypical meningioma morphology), loss of pattern (n = 4/9, seen in the chordoid menin-

Fig. 1 (A) Chordoid meningioma with eosinophilic tumour cells in cords and a mucoid matrix (hematoxylin-phoxyn-saffron: HPS, bar 100 μm). (B) Mucoid matrix of chordoid meningioma positive for Alcian Blue (Alcian Blue/HE, bar 100 μm). (C) Chordoid meningioma with focal area of necrosis (black arrows, HPS). (D) Tumor cells showing focal positivity with immunostain EMA (epithelial membrane antigen, black arrows). (E) Tumor cells showing focal nuclear positivity with PR (progesterone receptor antibody, black arrows) immunostaining. (F) Ki-67 proliferation index (MIB-1 antibody). In the example, Ki-67: 6.5% (calculated by using ImageJ).

© 2014 Japanese Society of Neuropathology

© 2014 Japanese Society of Neuropathology

50–60 30 100 80 100 100 50 60 95 100 100 100 0.6 2.5 0.8 2 N/A 0.8 2.8 4 0.7 6.5 N/A 4.6 2 2–7 6 4 N/A 1 7 4 1 0 0 2 Transitional Atypical None Atypical Atypical None Atypical Atypical Transitional None None None D D, N D D D, N D D D, B D D D D N Y N Y Y N Y Y N Y N Y B, brain; D, dura; F, focal; HPF, high power field; N, bone; N/A, not applicable.

YF YF N Y Y N Y Y N N N N YF YF Y N N N Y Y N N N N N N Y N N N N N N N N N YF YF N Y Y N Y Y Y N N Y YF YF N Y Y N Y Y Y N N Y 1 2 3 4 4R1 5 6 6R1 7 8 8R1 9

YF YF N N N N N N Y N N N

MIB-1 proliferation index (%) Mitotic count (per 10 HPF) Additional morphology Infiltration (B, D, N) Geographical necrosis Loss of pattern Nodules of high cell density Inflammation Cellular atypia (included nuclear atypia here) Small cells with high nuclear/ cytoplasm ratio Prominent nucleoli

Kepes et al. first devised the term “chordoid” in their case series, which included adolescents with Castleman’s disease, a rare lymphoproliferative disorder characterized by growth of a single lymph node or with systemic localization. CM remains a rare lesion that accounts for 0.32– 1.0% of all intracranial meningiomas.10,12,13 This was confirmed in our retrospective analysis of CM cases. Nine patients were reviewed from 1743 total meningioma patients in a 1995 to 2013 time period at St. Michael’s Hospital in Toronto. To the best of our knowledge, 221 cases of CM have been reported in the English literature worldwide in the form of single case reports and/or case series.2,3,6,8–10,12,14–72 A major predictive parameter of recurrence in atypical meningiomas is extent of surgical resection.73,74 Owing to its propensity to recur following STR, CM is classified as

Case no.

DISCUSSION 6

Table 2 Pathological description of primary chordoid meningioma tumors

gioma areas, as well as the areas showing atypical meningioma morphology), geographical necrosis (n = 5/9), infiltration of the brain (n = 1/9, seen only after recurrence), bone invasion (n = 2/9, one case occurred after recurrence), mitotic count (ranging from 0–7/10 HPF (high-power field)), automated MIB-1 labeling index (MIB-1 LI, ranging from 0.6% to 6.5%) and tumor percentage of chordoid features (Table 2). Additional morphology was present in 5/9 cases with 3/9 cases showing atypical meningioma histology with mitosis > 4/10 HPF and 2/9 cases showing transitional meningioma histology. Lymphocyte and plasma cell infiltration (inflammation) was noted solely in case 3. Recurrence occurred in 3/9 cases and the histological features most associated with recurrence included: necrosis (3/3 cases), increased mitosis (2/3 cases) and loss of pattern (2/3 cases) (Fig. 2). In one case of recurrence (case 6), tumor infiltration progressed from the dura matter to the brain. A large range of MIB-1 LI percentage of tumor specimens was observed (0.6–6.5%; mean 2.3%). The MIB-1 LI progressed from 2.8 to 4 in the recurrence for case 6. No correlation was found between the presence of Ki-67 and tumor recurrence; thus cases with higher MIB-LI, as seen in case 9, had no recurrence as opposed to recurring tumors with lower MIB-1. Percentage of chordoid features was calculated and ranged from 30% to 100% (mean 78.9%). In the cases of recurrent CM (cases 4 and 6) the percentage of chordoid features increased by 20% and 10%, respectively. The chordoid feature percentage of the third case of recurrence (case 8) remained 100%. In case 6, the mitotic count, the Ki-67 and the percentage of chordoid features increased in the recurrent tumor. In cases 4 and 8, the Ki-67 value was not available for the recurrent tumor; therefore, no comparisons were made.

141 Percentage chordoid features (%)

Chordoid meningioma

142

Fig. 2

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Histological features correlation with recurrence. , Cases; , No recurrence; , Recurrence.

WHO grade II meningioma.7 In contrast to typical meningiomas with a 10-year recurrence rate of 61% following STR,75 CM recurs quickly following surgery.2,3,8,9,38,61 The case series by Kepes et al. and other large case series reported a recurrence rate of 16–42%,2,6,9 while others reported higher61 and low or no rate of recurrence.10 We observe that recurrences occurred in 33.3% of patients within 1 year since the subtotal resection of the primary lesion. Since recurrence is related to extent of tumor resection, efforts to achieve total excision of the lesion should be a major objective of surgery. CM tumor cells demonstrate chords and clusters of eosinophilic cells arranged in a mucin-rich basophilic matrix, with cytoplasmic vacuolations. Authors hypothesized that the propensity for CM to recur and spread following STR could be related to the mucoid characteristics of the tumor,9,46,49 and consequently contribute to its tendency to regrow.24 In addition, others have noted that the mucoid quality may render the tumor difficult to adequately excise,48 although this correlation is still controversial. All the cases in our retrospective review had a mucoid background, irrespective of the recurrence. More efforts should be made in studying the biology of CM in relation to its propensity to recur. Couce et al.2 first quantified the percentage of chordoid features in CM tumors. The authors stated that 85.7% of recurrent tumors exhibited chordoid features greater than 50%.2 In another large series, disease progression was seen in five patients with primary features of 40–80%.9 Similarly, Mitsuhashi et al.43 and Donato et al.20 observed tumor recurrence characterized by high chordoid features percentage. A series of 17 cases stratified their histological specimens into two groups and found that recurrence occurred in 75% of patients exhibiting over 50% chordoid features, while a recurrence occurred in 20% of patients below the 50% mark.36 In contrast, no recurrence was seen in the case by Denaro et al.,19 who noted a high percentage

of chordoid features (80%). We noted a range in the percentage of chordoid features among our patient population from 30–100% (mean 78.88%), and an increase in chordoid morphology among tumors that recurred of 10% and 20%.The chordoid feature percentage of the third case of recurrence (case 8) remained 100%. The percentages of chordoid features are not consistently reported across the CM literature and consequently, it is difficult to establish a relationship between extent of chordoid patterns in primary lesions and tumor recurrence post-resection. The inter-observer variability of the quantification of the chordoid features is another aspect to be considered. Ki-67 is a nuclear protein that is associated with cellular proliferation, and can be readily employed as a prognostic factor of tumor recurrence and patient survival.76 Maier et al.77 noted a positive correlation between the MIB-LI and the classification grades of meningioma malignancy. Controversially, the classification of chordoid meningioma as WHO grade II has not consistently correlated with the incidence of mitotic figures, and maintains a wide range of degree of proliferation. Couce et al.2 noted that Ki-67 prevalence ranged from 0.4% to 11.4% (mean 5.2%). A large range of MIB-LI was seen in recurring tumors.2,8 Alternatively, others noted a narrow range of Ki-67 among their patients without recurrences.3 Wang et al.9 noted a narrow range of 1–10% (mean 2.0%) with no correlation with progression-free survival at 36 months. The MIB-1 LI ranged from 0.6% to 6.5% (mean 2.3%) in our patient population, which progressed from 2.8% to 4% in one instance of recurrence (case 6). No correlation was noted between Ki-67 and tumor recurrence, in concordance with the findings of others.9 We noted that recurring tumors had lower MIB-1 LI (2% and 2.8%). Much controversy exists regarding the use of MIB-LI in determining tumor recurrence and methodology for MIB-1 LI calculation. Currently, MIB-1-stained tumor specimens are scanned for the region of interest with many proliferative figures, denoted © 2014 Japanese Society of Neuropathology

Chordoid meningioma as the “hot spot method”. Thus, a degree of inter-observer variability may exist. Other authors have noted that there is a lack of significant data standardization across various research groups,76 rendering the definite correlation of Ki-67 to malignancy and recurrence quite difficult to assume. More efforts should be made to study the clinical utility of this marker of proliferation. Our literature summary concludes that CM has an anatomical preference for the supratentorial region (177/221: 80.1%). The finding is concordant with the work of others.2,3,8,9,60,61 Other CM cases occur in the infratentorial region and unusual sites, notably the ventricular system,3,15,48,56,64,65,78 the jugular foramen,60 the orbit,25,44,50,54 the cervical spine26,40,78 and the pineal region.21,23,27,35 A greater rarity is attributed to extracranial and extraskeletal CM, such as the lung.52,53 The most common presenting symptoms included gait disturbances and headache, the latter often related to the anatomical localization of the lesion and combined with other symptoms. Infiltration of the dura is common among our chordoid meningioma cases. Bone infiltration is less common and was noted in two patients, one after recurrence. Brain invasion was noted in one recurrence, and a discussion on the significance of brain invasion was undertaken in a recent review.9 Histological features most associated with recurrence in our cases included necrosis, increased mitosis and loss of pattern. No pediatric patients were noted at our institution. Meningiomas in general occur less often in the pediatric population as compared to the adult population.79,80 The age range of our patient population with CM was 19–85 years (mean 60 years), which is in accordance with the wide age range observed in several large case series.2,3,9,10,36,38,51 A female preponderance of CM is noted across the CM case report and series literature.9,61 One hundred and twenty were noted of the 221 reported cases, which comprise 54.3% of the CM patient population. At our single institution, we noted six women (66.7%) and three men (33.3%). To the best of our knowledge, no hypothesis has been stated with regard to a definite link between gender and recurrence of CM despite the slight preponderance of CM among women noted in our review of the medical literature. Much debate exists regarding the role for postoperative radiotherapy (RT) in cases of CM. Considerations for RT have been primarily for the patients of atypical meningioma having undergone total or subtotal resection,81–84 or benign meningiomas having undergone subtotal resection for tumor control and to reduce the risk for recurrence, with limited evidence.85 Other authors have recommended early RT in cases of atypical meningioma irrespective of the extent of resection.86 In cases of chordoid meningioma, authors favor radiotherapy.44,46 Nambiar et al.48 observed © 2014 Japanese Society of Neuropathology

143 the lack of recurrence of CM in a pediatric case given RT following tumor recurrence. Wang et al.9 noted higher incidence of recurrence in CM patients who did not undergo RT. The role of radiotherapy in atypical meningioma remains related to the extent of tumor resection, as well as to the physician and patient’s decision.87 The differential diagnosis for chordoid meningioma includes chordoid neoplasms such as chordoma, myxoid chondrosarcoma, metastatic mucinous carcinoma, chordoid glioma, and non-chordoid forms of meningioma with lymphoplasmacellular infiltrates,2 and can be made on the basis on immunohistochemical, cytological, ultrastructural and anatomical locale characteristics. Due to the high propensity to recur, the correct diagnosis of CM is of utmost clinical and pathological value.2,6,41 Immunohistopathological studies have shown that the tissue exhibits positivity for vimentin, epithelial membrane antigen (EMA) and D2-40, occasional positivity for S-100 protein, while demonstrating negativity for GFAP and cytokeratin.2,6,32 The tumor particularly resembles chordoma7 and a difficulty in diagnosis is noted.38 In contrast to CM, chordoma exhibits positivity to cytokeratin, EMA and minimal positivity to S-100,29,47,88,89 and negativity to D2-40.9,89,90 Chordoma is also positive for brachyury, a novel marker for chordoma, which is gaining interest due to its use in distinguishing chordoma from chordoid lesions.72,89 Moreover, despite the negativity to EMA and cytokeratin,91 chondrosarcoma exhibits positivity for D2-40 (a monoclonal antibody against popoplanin), S-100 and CK-20.8,9,89 Furthermore, mucinous carcinoma exhibits positivity to cytokeratin and it is possible to observe cytological atypia and intracellular mucin.27 Chordoid glioma exhibits positivity for S-100 and GFAP92,93 and is not durabased as opposed to meningioma.38,94 A panel of immunological markers is useful for correct histological differential diagnosis between meningeal tumor subtypes.Authors suggested EMA, GFAP and D2-40 to be the best markers for distinguishing between subtypes.90 In addition to the former markers, others suggested the utility of employing podoplanin, cytokeratins and CD10 markers.8 Recent researchers determined a more extensive immunohistochemical profile to stratify between overlapping chordoidlike tumors.89 The role of angiogenesis in chordoid meningiomas is not known yet, although some authors suggested the use of the vascular endothelial growth factor and the microvascular density as potential prognostic factors.71 Histological description of CM is common, and addresses primarily the nuclear-to-cytoplasm ratio, the presence or absence of prominent nucleoli, necrosis, calcification and, as commonality with cytological studies, size and architecture of cells, lymphoplasmacytic infiltrates, psamomma bodies, mitotic activity, chord-like organiza-

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tion, myxoid matrix and cellular whorl formation.9,36,51,66 In our series, we found heterogeneity in the proportion of pathological features across all cases. The combination of cytological descriptions with histopathological observations could prove indispensible in assuming a correct diagnosis of CM.61

CONCLUSION In our retrospective analysis, we identified nine chordoid subtypes over a case series of 1743 (0.52%) meningiomas. CM occurs primarily in the adult population, with preferential supratentorial anatomical localization and no systemic disease was noted. Efforts to totally excise the tumor should be a major objective of surgery to reduce the incidence of tumor recurrence. Tumor biology studies could provide insight into the propensity of CM to spread and recur. The percentage of chordoid features within the tumor specimen could assist in predicting the pathogenesis of the lesion. The correlation of the index of proliferation, quantified by means of Ki-67 positivity, to recurrence rate is still controversial. Much debate exists with regard to the role of adjuvant radiotherapy in CM cases. Immunohistochemical, cytological and ultrastructural studies could be used in combination to assure a correct diagnosis of CM. Owing to the rare occurrence of this meningioma subtype, larger case series are required to assist in providing reference for future diagnosis and improve the therapeutic management of chordoid meningioma.

CONFLICT OF INTEREST The authors declare no conflict of interest.

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