Pathological Spectrum of Dura-Based Nonmeningothelial Lesions: 5 Years' Experience from a Tertiary Care Centre

Abstract

Introduction  Nonmeningothelial lesions arising from the dura comprise a wide spectrum of pathologies ranging from neoplastic to infective etiologies. They have overlapping clinical and radiologic findings necessitating histopathological evaluation for the final diagnosis which in turn dictates management and prognosis. Therapeutic strategies are different for each of the lesion. There is scarcity of large case series detailing clinicopathological spectrum of dura-based nonmeningothelial lesions.

Materials and Methods  In this study, we analyzed the neuropathological spectrum of dura-based nonmeningothelial lesions diagnosed over a period of 5 years in our tertiary care center.

Results  There were 79 cases of dura-based nonmeningothelial lesions constituting 7.3% of all dura-based lesions (age range: 2–75 years; M:F = 2:3). Basal region was more frequently involved than the convexities. On histopathology, neoplastic lesions predominated (92.4%) and included in order of frequency solitary fibrous tumor/hemangiopericytoma (35.6%), gliomas (27.4%), metastasis (27.4%), mesenchymal tumors (4%), primitive neuroectodermal tumor (2.73%), and medulloblastoma (2.73%). Infective lesions were less frequent (7.6%), included fungal infections and Rosai-Dorfman disease.

Conclusion  Awareness of the spectrum of nonmeningothelial dural lesions is useful for pathologists as well as the treating surgeon.

Introduction

Meningiomas are the most common neoplasm involving the meninges ¹ and is the most frequent diagnosis considered in any dura-based lesion recognized on imaging. However, a wide variety of neoplastic and nonneoplastic lesions can occur in the dura or involve the dura that can mimic a meningioma on clinical and radiologic evaluation. ² The occurrence of neoplastic and nonneoplastic dura-based masses that mimic meningiomas has received little attention, and to the best of our knowledge, there are no large case series that document the clinicopathological spectrum of dura-based nonmeningothelial lesions. ³ Awareness about these meningioma mimics is essential in preoperative diagnosis and thus plan treatment strategies and post-treatment follow-up. The present study aims to document the clinicopathologic spectrum of dura-based nonmeningothelial lesions over a period of 5 years from a single Institution with relevant review of literature.

Materials and Methods

This is a retrospective study conducted in the Department of Neuropathology for a period of 5 years. The study included all intracranial dura-based lesions based on radiological or preoperative findings. Cases with exclusive bony involvement with only focal extension to the dura and sinonasal tumors with extension of tumor to dura were not considered ‘‘dural involvement’' for the purpose of this study. Cases with incomplete clinical and radiological details were excluded.

The demographic profiles, clinical presentation, radiological details, clinical diagnosis, and differential diagnosis considered, and preoperative findings were reviewed. All tissues were fixed in 10% neutral buffered formalin and was subjected to routine processing for paraffin embedding. Serial sections were cut at 4 µ thickness and routine staining was done with hematoxylin and eosin. Special stains for acid fast bacilli (Ziehl Neelsen stain), fungal hyphae (Gomori methenamine silver and periodic acid Schiff) were performed based on histopathological findings, and relevant immunohistochemistry (IHC) was performed using automated staining with Ventana Bench Mark based on the clinical, radiological, and histopathological differentials. IHC panel used included vimentin, epithelial membrane antigen (EMA), glial fibrillary acidic protein (GFAP), IDH1R132H, ATRX, K _i -67, STAT-6, CD99, synaptophysin, INI1, cytokeratin (CK), CK7, and CK20.

Results

Of the 5,158 intracranial tumors reported during the study period, 996 were meningiomas and 73 (92.4%) cases were dura based. This constituted 1.4% of all intracranial tumors and 6.8% of dura-based tumors. Apart from this, there were six infective/inflammatory lesions encountered in the study period (7.6%). Spectrum of lesions in order of frequency included solitary fibrous tumor/hemangiopericytoma (SFT/HPC), metastasis, glial tumors, primitive neuroectodermal tumor (PNET), mesenchymal nonmeningothelial tumors, fungal infections, and Rosai-Dorfman disease (RDD).

The median age of presentation was 40 years with an age range of 2 to 75 years. In total, 38% were male and 62% were female patients. The tumors most frequently occurred in the frontal location closely related to the meninges. In total, 52% of the cases were located in the basal region and 48% were in the convexity. The commonest pathological diagnosis in our study was SFT/HPC, which was also the commonest diagnosis in the adults. Among the pediatric patients (12% were pediatric), PNET was the commonest diagnosis.

Solitary Fibrous Tumor/Hemangiopericytoma

During the study period, there were 26 cases of HPC (35.6%), of which 30.8% (8/26) were grade II and 69.2% (18/26) of cases were grade III. Age of these patients ranged from 19 to 75 years (20–75 years in grade II and 19–58 years in grade III) with the mean age of 39 years. In this cohort, there were 14 males and 12 females with male: female ratio of 1.6:1 in both the grades.

Most common presentation was headache in 14, associated with vomiting in 10 patients. Radiological details were available in 24 of 26 patients. Almost all, except one case was considered radiologically as meningioma (primary diagnosis in 54% and as differential diagnosis in 27%). Hence, the misdiagnosis rate was 96.2%. Intraoperative diagnosis was meningioma in 71% of the cases. In all the cases, histopathology revealed a cellular vasoformative tumor composed of short-spindled cells, in lobules and sheets intersected by thin walled branching vessels (stag horn appearance). Mitosis was <5/10 high power fields in grade II tumors, and was brisk, along with areas of necrosis and hypercellularity in grade III tumors ( Fig. 1A and B ). All the HPC showed nuclear STAT6 immunoexpression ( Fig. 1C ).

Fig. 1.

Photomicrographs of a case of hemangiopericytoma with large enhancing solitary mass, based on right posterior temporal basal dura on sagittal magnetic resonance image ( A ) and nuclear immunopositivity for Stat-6 ( B , H&E, ×100; C , immunoperoxidase, ×200); metastatic carcinoma showing a right frontal enhancing mass, based on anterior falx with perilesional edema ( D , magnetic resonance imaging) clusters of epithelial cells ( E , H&E, ×100) and an embryonal tumor ( F , H&E, ×200). H&E, hematoxylin and eosin stain.

Glial Tumors

In our series, 20 cases of glial tumors were dura based, which constituted 1% (20/1,998 cases) of all gliomas and 27.4% of dura-based nonmeningothelial tumors diagnosed during the study period. Among these, 10 were glioblastomas (GBM), four gliosarcomas (GS), two anaplastic ependymomas, three cases of anaplastic astrocytomas, and one desmoplastic infantile ganglioglioma.

Of 10 GBM cases (1.8%; age range: 30–70 years), the differential diagnosis considered included metastasis, GS, and meningioma. Headache was the most common presentation (50%) in these patients followed by weakness, altered behavior, and irrelevant speech. Age range of this cohort was 30 to 70 years with 40% of cases in the 5th decade followed by 3rd decade (30%). There was predilection for frontal lobe. Histologically, these cases showed classical features of GBM ( Fig. 2 ).

Fig. 2.

Photomicrographs of a dura-based glioblastoma with a right temporal lesion which is isointense on T1W axial MRI ( A ) and hyperintense on T2W axial MRI ( B ). On T1W contrast MRI, the lesion shows heterogeneous enhancement with few areas of nonenhancement suggestive of necrosis ( C ). Coronal, T1W images show lesion located at middle cranial base, broad base on dura ( D ) with posterior extension and perilesional edema ( E ). Postoperative contrast computed tomography image shows good decompression of the tumor ( F ). On histopathology, the tumor is cellular composed of pleomorphic astrocytes ( G , H&E, ×200) with microvascular proliferation ( H , H&E, ×200) and necrosis ( I , H&E, ×200). H&E, hematoxylin and eosin stain; MRI, magnetic resonance imaging.

Four cases of GS were diagnosed during this study period. Two peaks were found one in the 2nd decade and other in the 6th decade. Tumors had glial and sarcomatous areas; sarcomatous areas were reticulin rich. GFAP highlighted the glial component and was negative in sarcomatous component. Vimentin highlighted both the components.

Two cases of anaplastic ependymoma presented as dura-based mass in the 1st decade.

One case of desmoplastic infantile ganglioglioma was found to be dura based intraoperatively, which was solid cystic lesion radiologically. Hence, meningioma and high-grade glioma were considered intraoperatively. Histology showed small neurocytic cells within a dense desmoplastic stroma and focal area of undifferentiated neuroepithelial cells.

Metastasis

In our series, we had 20 cases (27.4%) of dura-based metastasis constituting 6.8% of all the intracranial tumors. Age of these patients ranged from 25 to 70 years with mean age of 49.2 years. There was male gender predilection (M:F = 1.5:1). Radiologically, the diagnosis of metastasis was considered in 35% (7/20) as the primary diagnosis and as one of the differential diagnosis in 25% (5/20) of these cases. Diagnosis of meningioma was offered in 10% (2/20) of cases and considered as one of the differential diagnosis in 25% (5/20) of cases. There was frontal predominance. Most common histological subtype was adenocarcinoma (75% [15/20]) followed by squamous cell carcinoma (15% [3/20]). In 35% of the cases, the primary was known (four with breast carcinoma, two lung carcinomas, and one colon carcinoma; Fig. 1D ).

Ewing's Sarcoma/Primitive Neuroectodermal Tumor

During this study period, two cases of PNET (2.73%) were dura based (out of the total, 54 cases of cranial PNET diagnosed) and these patients were aged 40 years (female) and 4 years (male). Both the patients presented with headache. Preoperative differentials considered were PNET and HPC. Sections showed embryonal tumor with clusters and sheets of primitive cells. Abundant neuropil and Homer Wright rosettes were seen. Synaptophysin was diffusely positive and INI1 showed retained status ( Fig. 1E ).

Mesenchymal Tumors

Interestingly, we had three cases of mesenchymal chondrosarcoma (3/5,158) constituting 0.06% of intracranial tumors, and 4% of dura-based nonmeningothelial tumors. Age of the patients at diagnosis ranged from 7 to 52 years. They presented with seizures, headache, and vomiting. Both the radiologic and intraoperative diagnosis were meningioma. Histology showed cellular tumor with sheets of cells exhibiting vesicular nuclei and scant cytoplasm intersected into lobules by thin-walled vascular channels ( Fig. 3 ). Focal hemangiopericytomatous areas, chondroid areas, and calcification were also noted. Immunohistochemically, there was diffuse positivity for CD99, Vimentin and S100 (labeled chondroid areas), and negativity with synaptophysin and EMA establishing the diagnosis of extraskeletal mesenchymal chondrosarcoma.

Fig. 3.

MRI shows a heterogeneous right frontal solitary lesion ( A , T2W, axial) with multiple cystic areas ( B , T2W, sagittal). Contrast MRI shows enhancement with few areas of nonenhancement ( C , axial) and broad base on dura ( D , coronal and E , sagittal). Postoperative contrast computed tomography image shows good excision of the tumor with mesh cranioplasty ( F ). Histopathology shows the tumor composed of round cells interspersed with hyaline cartilage ( G , H&E, ×40) and hemangiopericytomatous pattern of arrangement ( H , H&E, ×100). H&E, hematoxylin and eosin stain; MRI, magnetic resonance imaging.

Embryonal Tumors

There were two cases (2/165 [1.2%]), one was a 2-year-old female and the other was a 29-year-old male. Both presented with headache and vomiting. Imaging showed a posterior fossa mass lesion which was broad based on dura. Tumor was hypointense on T1 weighted and hyperintense on T2-weighted imaging, enhancing heterogeneously on contrast with a clear plane between the lesion and the cerebellum, and a diagnosis of meningioma was entertained radiologically with an alternate possibility of medulloblastoma. Histopathology revealed features characteristic of a desmoplastic medulloblastoma.

Rosai-Dorfman Disease

Apart from dura-based nonmeningothelial tumors, the most common inflammatory lesion was RDD. There were four cases that radiologically and intraoperatively closely mimicked meningioma. Histology showed dense infiltration by aggregates of lymphoid cells, histiocytes, lymphocytes, and plasma cells. Emperipolesis was also documented in all these cases ( Fig. 4 ). Histologically, they mimicked lymphoplasmacytic meningioma.

Fig. 4.

A case of Rosai-Dorfman disease shows right cerebro-pontine angle enhancing mass on axial MRI. The lesion is based on right petrous dura with extension on either side of internal acoustic meatus ( A ). There were multiple dural based lesions with uniform enhancement on contrast ( B ). The lesion is composed of lymphohistiocytic infiltrate ( A , H&E, ×100) with prominent emperipolesis ( B , H&E, ×200). The cells are immunopositive for S-100 ( C , immunoperoxidase, ×200) and CD68 ( D , immunoperoxidase, ×400). H&E, hematoxylin and eosin stain; MRI, magnetic resonance imaging.

A single case of fungal etiology was diagnosed in a 33-year-old male who presented with cranial nerve palsy. Magnetic resonance imaging revealed a lesion in right middle cranial fossa with dural tail, which were hypointense on T1 weighted and hyperintense on T2-weighted images. There was homogeneous contrast enhancement closely mimicking a meningioma. Histopathology revealed granulomatous inflammation with several giant cells within which were branching septate fungal hyphae morphologically consistent with aspergillus ( Fig. 5 ).

Fig. 5.

MRI brain (coronal) shows a solitary enhancing mass involving the right middle cranial fossa with sellar extension ( A ). MRI brain (axial) shows right middle cranial fossa mass involving the entire right middle cranial fossa with posterior fossa extension ( B ). Photomicrographs show a necrotizing granulomatous inflammation ( A , H&E, ×100) with acute angle branching septate fungi ( B , periodic acid Schiff, ×200). H&E, hematoxylin and eosin stain; MRI, magnetic resonance imaging.

Discussion

Dura-based lesions form an important group of intracranial pathologies with meningioma being the most common . A variety of the neoplastic processes involving the dura arise from the various dural components. ³ Also, many nonneoplastic and secondary CNS lesions are known to involve the dura. The spectrum of such lesions is wide ranging from nonneoplastic infective etiologies to tumors which closely mimic (clinically and radiologically) meningioma. The nonneoplastic lesions encompass both noninfectious and infectious etiologies, such as tuberculosis and sarcoidosis. Neoplastic processes include SFT/HPC, embryonal tumors, and metastatic lesions. However, the occurrence of these neoplastic and nonneoplastic dura-based masses has received little attention despite several case reports. To the best of our knowledge, there has been no case series from India. A brief review of the dura-based lesions is presented below with an attempt to create awareness, improve the understanding, and expand the knowledge related to these lesions.

In the present study, SFT/HPC constituted 27.8% of all the dura-based lesions and formed the commonest dura-based nonmeningothelial neoplasm. SFT/HPC are uncommon neoplasm representing approximately 0.4% of primary brain tumors and 2 to 4% of meningeal tumors, mainly affecting middle-aged patients. ⁴

Intracranial HPCs were first described in 1954 by Begg and Garret. ⁵ Earlier HPC from the meninges was described as an angioblastic meningioma and reclassified as a distinct pathologic entity in the World Health Organization classification. HPCs mimic meningiomas in their clinicoradiologic features, and most of the studies have shown low diagnostic rates on imaging, similar to our results. ⁶ In our study, the diagnosis of meningioma was considered radiologically either as the main diagnosis (54%) or as differential diagnosis (27%). HPC was the radiological diagnosis in only one case, and hence, the misdiagnosis rate was 96.2%. HPC should be differentiated from meningiomas as the former is believed to be more aggressive than meningiomas, notorious in the tendency to recur, and metastasize. Hence, correct diagnosis is critical for management. In addition to IHC markers such as EMA and CD34, STAT-6, which is seen in HPC, is a specific marker for the diagnosis.

The other category of CNS tumors that may present as dura-based lesion/mass are the glial tumors. GS is a variant of GBM, accounts for 2% of all the GBM. Often GS are known to involve the leptomeninges and the dura, with a sharp circumscription from the surrounding parenchyma, thus mimicking a meningioma. Intraoperatively, due to very firm nature of the tumor and encapsulation, most common diagnosis made intraoperatively is a tumor of meningeal origin. ⁷ GBM are usually intraparenchymal tumors, but on occasions when fed by the vessels of dura mater, the enhanced dural tail sign results in the radiologic misdiagnosis of meningioma. ⁸ It is hypothesized that the tumor spreading into the subarachnoid or subdural space is the possible cause of a dural tail in GBM on imaging. In the present study, GS constituted 4.5% of the dura-based nonmeningothelial tumors.

Metastasis to the dura is a rare manifestation, constituting 9% of the all central nervous system metastases in a study by Meyer and Reah. ⁸ On imaging, they tend to mimic meningioma due to increased signals on T2-weighted MR images and often with an enhancing dural tail. ⁹ The tumors which present with dural metastasis include carcinoma of the breast, prostate, lung, stomach; neuroblastoma, Hodgkin disease, non-Hodgkin lymphoma, and melanoma. The tumor may spread through hematogenous route as in lung carcinoma or by direct extension from calvarial metastases as seen with lung, cervical, some prostatic, and breast carcinomas. Hematogenous spread of cancer cells to dura is seen with lung cancer. In total, 25.5% of the dura-based lesions in our study were metastatic carcinomas. In our series, source of primary included breast carcinoma, lung carcinoma, and colon carcinoma. Most of these patients were middle aged and elderly. It is essential to suspect metastasis particularly in the elderly.

Among children, Ewing's sarcoma may present as dura-based mass. The PNETs/Ewing's sarcoma are more common in children (15–25% of CNS tumors) compared with adults. ¹⁰ When the tumor presents as a local dura-based mass, it tends to mimic a meningioma. However, PNET may also diffusely involve the leptomeninges without a primary mass within the parenchyma. In our study, PNET constituted 2.73% of all the dura-based tumors. In one case, the diagnosis of PNET was made radiologically. Hence, in all children with a dura-based lesions, PNET needs to be one of the differentials.

Mesenchymal chondrosarcoma was the other nonmeningothelial dura-based mass encountered in our study. Primary intracranial chondrosarcomas account for 0.16% of intracranial neoplasms. Most often, they arise from the skull base, but rarely chondrosarcomas have been documented to be primarily meningeal involving falx or the tentorium. The cell of origin of chondrosarcoma in the meninges has been postulated to be a multipotent mesenchymal cell or the meningeal fibroblasts. The tumor is aggressive in behavior. Hence, the histopathological diagnosis is important, and this tumor should be considered in the differential diagnosis of an enhancing mass in the frontoparietal region, especially in adolescent and young adult patients.

Nonneoplastic lesions such as RDD, plasma cell granuloma, and infections were also seen to present as dura-based mass. CNS involvement is rare. The patients present in the 4th decade with seizure, or cranial nerve deficit, depending on the site of involvement. It may present as a solitary dura-based lesion (common) or as multiple intracranial lesions. Intracranial RDD can be a diagnostic challenge because of its morphologic similarities to both benign and malignant processes. Intracranial RDD usually manifest on imaging as one or more enhancing, dura-based, extra-axial masses with perilesional cerebral edema, thus mimicking meningioma clinically and radiologically. ¹¹ Infections, most commonly fungal granulomas or tuberculous granulomas with extensive fibrosis can also present as dura-based mass. The diagnosis of fungal etiology is crucial from therapeutic perspective. Histopathological examination is essential in the accurate diagnosis of these conditions.

Role of Histopathological Examination

The above mentioned lesions radiologically and clinically mimic meningioma; hence, the final diagnosis depends on histopathologic examination. Hence, a systemic morphological/phenotypic evaluation aided by special stains and IHC is of paramount importance in accurate diagnosis. For example, on histology, SFT/HPC forms a close differential to fibrous meningioma composed of spindle shaped cells. In presence of staghorn vasculature and lack of whorls, pseudoinclusions favor a diagnosis of HPC. On IHC the tumor cells are positive for STAT-6, CD34, negative for EMA, and S-100. Metastasis is characterized by nests of epithelial cells, which are labeled by CK. GBM and GS may have a spindle cell component resembling other mesenchymal tumor, but the presence of glial component guides their diagnosis.

So, in the evaluation of these nonmeningothelial dural lesions, pathologic sampling forms the most critical step. Recognizing these lesions on radiology is a challenge. These lesions have to be considered in the list of differential diagnosis during radiologic and clinical assessment of dura-based lesions, especially with nonclassical features, atypical location, and presentation.

In conclusion, an increasing number of neoplastic and nonneoplastic lesions can occur and are being recognized in the list of dural lesions, and these have expanded the differential diagnosis of meningiomas. Awareness and knowledge about these lesions will enable correct diagnosis and high index of suspicion will facilitate their recognition pre/intra/postoperatively aiding accurate management. The present study has described the spectrum of neuropathological dura-based nonmeningothelial lesions and attempted to review the characteristics of these rare nonmeningothelial lesions of the dura that mimic meningiomas. This study describes the spectrum of dura-based nonmeningothelial lesions in an Indian population, and this may vary depending on the geographic location.

Funding Statement

Funding None.