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Are Meningeal Hemangiopericytoma and Mesenchymal Chondrosarcoma the Same?
A Study of HEY1-NCOA2 Fusion

Karen J. Fritchie MD, Long Jin, Ana Ruano MD, Andre M. Oliveira MD, PhD, Brian P. Rubin MD, PhD
DOI: http://dx.doi.org/10.1309/AJCPGUNGP52ZSDNS 670-674 First published online: 1 November 2013


Objectives: Meningeal hemangiopericytoma (HPC) and mesenchymal chondrosarcoma are aggressive neoplasms with a propensity to involve the meninges and dura. In addition to similar clinical presentations, both meningeal HPC and mesenchymal chondrosarcoma share overlapping morphologic features, including ovoid cells, variable collagen deposition, and a branching vascular pattern. Recently, a novel HEY1-NCOA2 fusion was reported as a recurrent event in mesenchymal chondrosarcomas.

Methods: Thirteen mesenchymal chondrosarcomas and 18 meningeal HPCs were identified from surgical pathology archives, and the tumors were evaluated for HEY1-NCOA2 fusion with reverse transcriptase–polymerase chain reaction (RT-PCR).

Results: HEY1-NCOA2 fusion transcript was detected in all six cases of mesenchymal chondrosarcoma but in none of the meningeal HPC cases (0/11) that were evaluable with RT-PCR.

Conclusions: These results show that (1) meningeal HPC and mesenchymal chondrosarcoma are distinct at the molecular level, and (2) the identification of HEY1-NCOA2 can be used as an auxiliary diagnostic tool to differentiate these entities.

Key Words:
  • Meningeal hemangiopericytoma
  • Mesenchymal chondrosarcoma
  • HEY1-NCOA2

Meningeal hemangiopericytoma (HPC) is an aggressive neoplasm characterized by high rates of local recurrence and extracranial metastases.1 Mesenchymal chondrosarcoma is a tumor that may involve both skeletal and extraskeletal sites but has a predilection for the meninges.2 In addition to similar clinical presentations, both meningeal HPC and mesenchymal chondrosarcoma share overlapping morphologic features, including oval to slightly spindled cells, variable collagen deposition, and a branching, staghorn vascular pattern. Recently, a novel HEY1-NCOA2 fusion was reported as a recurrent event in mesenchymal chondrosarcoma.3 Given the significant clinical and morphologic overlap between mesenchymal chondrosarcoma and meningeal HPC, we analyzed a group of the latter to determine whether they also harbored the HEY1-NCOA2 fusion.

Image 1

Morphologic and immunophenotypic features of mesenchymal chondrosarcoma and meningeal hemangiopericytoma (HPC). A, Low-power view of mesenchymal chondrosarcoma showing biphasic pattern of hyaline cartilage and cellular ovoid cell population. B, At medium power, the cellular component of mesenchymal chondrosarcoma shows primitive ovoid to round cells surrounding branching vessels. C, Low-power view of meningeal HPC shows closely packed cells surrounding staghorn-shaped vasculature. D, The lesional cells of meningeal HPC are ovoid to spindled with high nuclear-cytoplasmic ratios.

Materials and Methods

Case Selection

This study was approved by the Institutional Review Board at the Mayo Clinic. A total of 13 cases of mesenchymal chondrosarcoma and 18 cases of meningeal HPC with available formalin-fixed, paraffin-embedded tissue were selected from the Mayo Clinic (Rochester, MN) and Cleveland Clinic (Cleveland, OH) anatomic pathology database from January 1, 1987, to December 31, 2012. Mesenchymal chondrosarcoma cases contained a biphasic pattern of ovoid cells surrounding a variable branching vascular pattern adjacent to areas of well-differentiated cartilage Image 1A, Image 1B. Cases of meningeal HPC were dural-based lesions composed of closely packed ovoid to spindled cells associated with staghorn-shaped blood vessels Image 1C, Image 1D.

Control cases included three chondroblastomas, two chondromyxoid fibromas, five Ewing sarcomas, and five synovial sarcomas from the Mayo Clinic archives.


Total RNA was extracted from fresh-frozen paraffin-embedded (FFPE) tissue sections with Trizol Reagent kit (Invitrogen, Life Technologies, Grand Island, NY). Decalcification was performed for most FFPE tumor tissues before RNA extraction. Reverse transcriptase–polymerase chain reaction (RT-PCR) was used to detect HEY1 exon 4–NCOA2 exon 13 fusion transcripts using a specific primer set (forward: 5′-CGA GAT CCT GCA GAT GAC CGT GG and reverse: 5′-GCA CCA GTT GGG CTT TGC AAT GTG). The housekeeper gene PGK RT-PCR was run on all samples to check the RNA quality. PCR products were checked on 3% agarose gel electrophoresis. All PCR-positive results were confirmed with DNA direct sequencing.


Thirteen cases of mesenchymal chondrosarcoma were identified (9 females, 4 males) with patients ranging in age from 19 to 54 years (median, 34.3 years). Eighteen cases of meningeal HPC were identified (8 females, 10 males) with patients ranging in age from 24 to 73 years (median, 49.8 years). Six of the mesenchymal chondrosarcoma cases were primary tumors, 4 were recurrences, and 2 were metastases. For the cases of meningeal HPC, 12 cases were primaries, 4 were recurrences, and 2 were metastases. The sites of mesenchymal chondrosarcoma included both bone and soft tissue locations, whereas all of the primary and recurrent meningeal HPCs involved cranial sites Table 1.

HEY1-NCOA2 fusion transcript was detected in all six cases of mesenchymal chondrosarcoma Image 2A, Image 2B but in none of the meningeal HPC cases (0/11) that were evaluable Image 3. In seven cases each of mesenchymal chondrosarcoma and meningeal HPC, RT-PCR was uninformative because of RNA degradation. All controls (chondroblastomas [0/3], chondromyxoid fibromas [0/2], Ewing sarcomas [0/5], and synovial sarcomas [0/5]) were negative for HEY1-NCOA2 fusion transcript.


In 1928 Bailey and colleagues4 introduced the term angioblastic meningioma to describe a subset of meningeal based–lesions characterized by more aggressive behavior compared with conventional variants of meningioma. Three years later, Bailey and Bucy5 elaborated on the histologic features and described this subtype as “very cellular,” with easily identified mitotic figures and “numerous large and small spaces.” In 1935, Bergstrand and Olivecrona6 reviewed a series of 124 intracranial meningiomas and found four additional cases with a histologic appearance similar to those described by Bailey et al.4 Although the biologic behavior of these angioblastic meningiomas was difficult to assess due to incomplete resection and short clinical follow-up, the authors did acknowledge rapid growth and proposed alternative names, such as myoma malignum and malignant meningioma.

View this table:
Table 1
Image 2

2 Identification of HEY1-NCOA2 in cases of mesenchymal chondrosarcoma with reverse transcriptase–polymerase chain reaction (RT-PCR). A, Cases 3, 4, 9, and 11 had amplifiable RNA and showed the presence of HEY1-NCOA2. RT-PCR in the remaining cases was uninformative secondary to RNA degradation. B, Partial sequence of the HEY1-NCOA2 fusion transcript from case 9. bp, base pairs.

Image 3

HEY1-NCOA2 was not detected in any cases of meningeal hemangiopericytoma (cases 14–21 shown here). bp, base pairs.

Stout and Murray7 introduced the term hemangiopericytoma in 1942 for a soft tissue–based lesion thought to be derived from pericytes. Begg and Garret8 reported the first HPC of the meninges in 1954, while acknowledging that prior cases of angioblastic meningioma likely also represented this entity. In 1958, Fisher and coworkers9 described an additional case of meningeal HPC arising in the left temporal region of a 24-year-old male patient. In this instance, the tumor exhibited rapid growth with recurrence and eventually proved to be fatal. Simpson10 later proposed that these tumors be called simply “undifferentiated sarcoma” because of their aggressive behavior and uncertain lineage.

Over time the diagnosis of HPC at extracranial sites began to fall out of favor as pathologists recognized that HPC is a nonspecific morphologic pattern rather than a distinct entity. It was recognized and accepted that the majority of tumors previously diagnosed as soft tissue HPCs were best classified as solitary fibrous tumors. The story within the central nervous system is equally complex. Although the link between meningeal HPC and meningeal-based solitary fibrous tumors was questioned, they seemed to be distinct biologic entities. They exhibited drastic differences in clinical behavior, with solitary fibrous tumors behaving like their soft tissue counterparts, whereas meningeal HPC often portended a grim prognosis.1113

Mesenchymal chondrosarcoma is a rare sarcoma first described in 1959 by Lightenstein and Bernstein.14 It has a biphasic appearance consisting of hyaline cartilage matrix adjacent to primitive round cells. Although initially thought to be of chondroid derivation or possibly related to Ewing sarcoma,2 Wang et al3 reported the identification of a novel recurrent HEY1-NCOA2 gene fusion in mesenchymal chondrosarcoma.

Although mesenchymal chondrosarcomas occur at various bone and soft tissue sites, they have a predilection for the head and neck region, including the meninges/dura. Mesenchymal chondrosarcoma typically occurs in young adults between the ages of 15 and 35 years,2 whereas meningeal HPCs show a similar but slightly older age distribution (mean age, 43 years).15 Both tumors also behave somewhat unpredictably with potential for local recurrence and distant metastases. Besides significant clinical overlap, both mesenchymal chondrosarcoma and meningeal HPC share morphologic features. Even though mesenchymal chondrosarcomas typically have a cartilaginous component not seen in meningeal HPCs, the cellular component of both tumors is similar and characterized by a densely packed round to ovoid cell population with variable mitotic activity surrounding a prominent branching staghorn vascular pattern. The immunoprofile of mesenchymal chondrosarcoma and meningeal HPC is inconsistent, and there is no reliable immunohistochemical marker for either tumor.

Given the striking clinical and histologic likeness between meningeal HPC and mesenchymal chondrosarcoma, we postulated that both tumors may belong to the same biologic entity, with meningeal HPC representing a variant of mesenchymal chondrosarcoma lacking matrix production. However, our results argue that these two tumors are indeed distinct entities that are not related at the molecular level. Interestingly, recent work has shown that meningeal HPC harbors the NAB2-STAT6 fusion, which has also been identified in solitary fibrous tumors, suggesting that these entities are linked genetically after all.1618

Our findings also suggest that pathologists are currently relatively proficient at distinguishing meningeal HPC and meningeal-based solitary fibrous tumor, and the finding of well-differentiated cartilage is a helpful histologic discriminator. However, this may not have always been the case. Interestingly, in their 1958 case report, Fisher et al9 described “rare foci of immature cartilage and osteoid.” In a series of eight HPCs of the meninges by Kruse19 in 1961, the eighth case contained “foci of cartilaginous and osteoid tissue.” It is possible that these cases thought to represent meningeal HPCs were actually mesenchymal chondrosarcomas.

In summary, although mesenchymal chondrosarcoma and meningeal HPC exhibit clinical similarities and both contain a primitive round cell component, they are distinct at the molecular level. On large biopsy or complete resection specimens, the presence of a cartilaginous component is key in correct classification. However, on smaller biopsy specimens, the identification of HEY1-NCOA2 fusion may be a helpful ancillary tool for accurate diagnosis.


Upon completion of this activity you will be able to:

  • describe the clinical and morphologic features of mesenchymal chondrosarcoma and meningeal hemangiopericytoma.

  • use morphologic and molecular findings to differentiate mesenchymal chondrosarcoma and meningeal hemangiopericytoma.

The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.

The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Questions appear on p 756. Exam is located at www.ascp.org/ajcpcme.


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