Dural composite hemangioendothelioma: The first intracranial case

Abstract

Background:

Composite hemangioendothelioma (CHE) is a rare, locally aggressive neoplasm of intermediate malignant potential. It is composed of a mixture of vascular tumors with a predilection for the dermis and subcutis of the extremities.

Case Description:

In this report, we describe a 41-year-old man who presented with a 2-month history of headache, dizziness, and intermittent seizures. Magnetic resonance imaging showed a hemorrhagic, multilobulated, and dural-based mass with extension into the calvarium. The mass measured 10.3 × 4.8 × 4 cm along the interhemispheric fissure and encased the superior sagittal sinus. Excision was performed, and histopathologic examination revealed a heterogeneous mixture of vascular components consisting of epithelioid hemangioendothelioma, retiform hemangioendothelioma, and hemangioma. This is the first report of a primary intracranial CHE.

Conclusion:

The spectrum of mesenchymal neoplasms within the cranium expands to encompass CHE.

INTRODUCTION

Hemangioendotheliomas are vascular neoplasms that exhibit an intermediate level of malignancy and display histopathological characteristics that fall between those of a hemangioma and an angiosarcoma. They are located predominantly in the skin and subcutaneous tissue of the distal extremities. Although they can be locally aggressive, they rarely metastasize. They encompass a diverse spectrum of histologic types, including epithelioid hemangioendothelioma (EHE), retiform hemangioendothelioma (RHE), papillary intralymphatic angioendothelioma, pseudomyogenic hemangioendothelioma, kaposiform hemangioendothelioma (KHE), and composite hemangioendothelioma (CHE).[96]

CHE refers to a rare neoplasm of intermediate malignant potential composed of two or more of the following tumors: EHE, RHE, papillary intralymphatic angioendothelioma, KHE, and angiosarcoma. Well-differentiated vascular lesions, such as hemangiomas and arteriovenous malformations, may also be found in CHE. Very few cases of CHE have been described in the literature, and they usually involve the skin or soft tissue.[96] Here, we present the first case report of an intracranial primary CHE arising along the falx cerebri with infiltration into the calvarium. It is crucial to report this locally aggressive neoplasm due to its clinical presentation and radiographic similarity to other neoplasms such as meningioma. In this report, we also provide reviews of published CHE cases and primary intracranial hemangioendothelioma cases.

CASE HISTORY

The patient is a 41-year-old right-handed man who presented to an ophthalmologist with diplopia for the prior two months. He had also been experiencing intractable headaches, dizziness, and intermittent seizures manifesting as shaking of his right leg, with each episode lasting 2–3 min. These symptoms had steadily progressed, prompting him to seek medical consultation. He denied any previous similar episodes or any significant medical history. Although there was full vision of the left eye, there was right nasal hemianopsia with superior field cuts. He was sent to the emergency department for evaluation of bilateral papilledema.

A baseline head computed tomography (CT) scan showed a lobulated hyperdense soft-tissue mass along the interhemispheric fissure and superior sagittal sinus (SSS) [Figures 1a and b]. Mass effect was noted on both parietal lobes with mild inferior tentorial herniation. Vasogenic edema surrounded the mass in the posterior left parietal lobe, and permeative lytic involvement of the parietal calvarium was also noted. The SSS was fully encased within the mass. Magnetic resonance imaging (MRI) of the brain with and without gadolinium demonstrated a large, hemorrhagic, and multilobulated enhancing mass measuring 10.3 × 4.8 × 4 cm (anteroposterior × transverse × craniocaudal dimensions) along the interhemispheric fissure encasing the SSS with possible sinus occlusion [Figures 1c and d]. There was biparietal calvarium involvement, including the inner and outer tables extending into the subgaleal soft tissues [Figure 1e].

Figure 1:

Baseline noncontrast computed tomography and magnetic resonance imaging (MRI) images of the brain. (a) Coronal view shows an interhemispheric mass with left-sided mass effect. (b) Axial view using bone window reveals lytic involvement of calvarium. (c) Axial T2-weighted MRI shows superior sagittal sinus involvement. (d) Coronal T2-weighted MRI reveals tumor extension through the calvarium. (e) Sagittal T1-weighted MRI post-gadolinium shows tumor enhancement.

The patient was sent for a formal angiography procedure after identifying possible SSS occlusion on MRI. There was a postangiography procedure diagnosis of partial occlusion of the posterior second third of the SSS with collateral drainage primarily to the left side through cortical veins (not shown). Artery embolization was not feasible, given the location of the neoplasm relative to the SSS. Based on the clinical presentation and neuroimaging, the decision was made to take the patient for a bilateral frontoparietal craniectomy for tumor resection. Gross appearance during surgery revealed a hard, fibrous mass with marked vascularity (not shown). The neoplasm seemed to originate from dura overlying the SSS, tracking along the interhemispheric fissure and extending to the surrounding cranium (not shown). Creating planes among the mass and parenchyma was difficult due to the adherent nature of the neoplasm. Gross total resection was limited by the location of the neoplasm involving a substantial part of the SSS and the anterior paracentral lobule. Once larger portions of neoplasm located away from eloquent areas were excised, careful attention was turned to debulking the remaining neoplasm with the use of the Cavitron Ultrasonic Surgical Aspirator. The patient experienced an uncomplicated 2-week postoperative course before being sent to inpatient rehabilitation and then Gamma Knife radiotherapy for residual tumor.

Pathology

Histopathological examination of the neoplasm showed an admixture of different components with focal infiltration into the dura and bone. Approximately 30% of the neoplasm had abundant eosinophilic cytoplasm, nuclear atypia, and intracytoplasmic vacuoles with occasional hyalinized stroma, consistent with EHE [Figure 2a]. Many areas of the neoplasm (approximately 50%) consisted of long, branching, and thin-walled blood vessels with monomorphic cells that protruded into the lumen, occasionally forming a hobnail pattern consistent with RHE [Figure 2b]. In focal areas (approximately 20% of the examined neoplasm), markedly dilated thin-walled vascular channels were lined by bland, oval nuclei [Figure 2c]. No angiosarcoma-like areas or KHE -like areas were identified. Many of the tumor cells were strongly positive for CD31 [Figure 2d] and ERG [Figure 2e] by immunohistochemistry. Mitotic figures were rarely seen (not shown). No necrosis was evident (not shown). The Ki-67 proliferation index was variably mildly elevated [Figure 2f].

Figure 2:

Histologic features of the intracranial composite hemangioendothelioma. (a) Hematoxylin and eosin (H&E)-stained section shows an area of epithelioid hemangioendothelioma, with cells containing intracytoplasmic vacuoles embedded in a hyaline stromal matrix. (b) H&E-stained section shows an area of retiform hemangioendothelioma, with abundant arborizing vascular channels. (c) H&E-stained section shows an area of hemangioma, with dilated vascular channels lined by oval nuclei without atypia. (d) An anti-CD31 antibody reveals abundant endothelial cells in this neoplasm. (e) An anti-ERG antibody confirms the abundant endothelial cells in this neoplasm. (f) The Ki-67 proliferation index is low, with up to 3.6% of cells labeled with this antibody.

DISCUSSION

Here, we present the first case report of a primary intracranial CHE in a 41-year-old man who presented with headache, dizziness, and seizures. On initial presentation and baseline CT and MRI [Figure 1], the preoperative planning was anticipatory for meningioma arising from the falx cerebri and invading the calvarium. The intraoperative findings seemed to be incongruent with that of a meningioma, given the high vascularity and adherent nature of the neoplasm. Histopathologic examination of the resected mass revealed a heterogeneous mixture of vascular lesions, including RHE (major component), EHE, and hemangioma. The expression of the vascular endothelial cell markers CD31 and ERG further supported the diagnosis of CHE [Figure 2]. This patient prompted us to review published intracranial hemangioendothelioma cases, which revealed that EHE is by far the most common hemangioendothelioma. Our report widens the spectrum of primary vascular tumors arising in the central nervous system.

First described in 2000, CHE is a rare, intermediate grade slowly growing vascular lesion that usually presents as an erythematous nodule in the dermis or subcutaneous tissue of the extremities. Less than 100 cases have been reported in the literature [Table 1].[4,5,8,11-13,15,18-21,25,28,31,32,36,39,41,46,48-52,55,56,58,60,61,69,74,75,77,80,81,87,88,90,91,93,100,102,103] Two patients with primary spinal CHE have been reported.[58,60] The reported median age at diagnosis is 42.5 years, which is nearly identical to our patient’s age. Risk factors for CHE include Maffucci syndrome, lymphedema, and a history of radiation therapy. There are varying combinations of vascular components, including hemangioma, arteriovenous malformation, EHE, RHE, papillary intralymphatic angioendothelioma, KHE, and angiosarcoma. As in our patient, the predominant components have been reported to be RHE and EHE.[31,61]

Table 1:

Summary of reported composite hemangioendothelioma.

In comparison to conventional angiosarcoma, most CHEs exhibit less aggressive behavior. However, adjuvant therapy may be warranted in cases of subtotal resection, given the rate of local recurrence and malignant potential.[96] A subtotal resection or biopsy may also not provide an accurate, full representation of the entire neoplasm. Therefore, it is likely that CHE is under-reported in the literature.

Since EHE is a common component of CHE,[31,61] it is an important entity in the differential diagnosis. EHE typically originates outside the neuraxis, involving skin, soft tissue, solid organs, and bones. This vascular neoplasm of intermediate malignant potential is often arranged in clusters and cords embedded in a myxo hyaline stromal matrix. The tumor cells are epithelioid and have characteristic intracytoplasmic vacuoles that represent immature vascular lumina. Immunohistochemical analysis reveals the expression of endothelial differentiation markers such as CD31, ERG, CD34, and FLI1.[96] A review of the literature revealed 61 cases of primary intracranial EHE [Table 2].[2,3,6,7,9,10,16,18,23,26,27,29,30,33,35,38, 40,43,45,47,53,54,57,59,62-68,70-73,76,79,82-86,89,92,94,95,98,99,101,104,105] There is a wide age range (31 weeks gestation-74 years of age), with a slight male predilection (31:30). Parajón et al. and Murali et al. published case reports with reviews of reported intracranial EHEs.[59,67] Their work showed a 24% (8/34) recurrence rate, with three cases having subtotal resections. In a follow-up period ranging from 4 weeks to 11 years, five patients were represented with neoplasms affecting extracranial sites.

Table 2:

Summary of reported primary intracranial epithelioid hemangioendothelioma.

The other common component in CHE, seen in our patient’s tumor, is RHE.[31,61] Like EHE, RHE occurs primarily in young and middle-aged adults and demonstrates a tendency for frequent local recurrence and rare metastasis. The clinical manifestation of RHE often presents as a solitary reddish lesion in the dermis or subcutis of the extremities. Histopathological examination reveals a distinctive pattern characterized by arborizing blood vessels that resemble the rete testis. These blood vessels are lined by relatively uniform endothelial cells that may exhibit a hobnail pattern. While endothelial cell markers are expressed, lymphatic markers such as podoplanin/D2-40 are negative.[96] A review of the literature revealed five cases of reported primary intracranial RHE [Table 3].[1,34,44,89] There is a wide age range (1–62 years of age), with a slight female predilection (3:2). Four of the five cases showed tumors originating in bone. No recurrence was seen in the two cases with reported outcomes.

Table 3:

Summary of reported primary intracranial retiform hemangioendothelioma.

Other hemangioendotheliomas may occur within the cranium. Single cases of intracranial pseudomyogenic hemangioendothelioma[97] and papillary intralymphatic angioendothelioma[78] have been reported. More common is intracranial KHE, seen exclusively in young males and often associated with dura [Table 4].[14,17,22,24,37,42,89] KHE usually presents in children with the Kasabach-Merritt phenomenon as an infiltrative mass containing capillaries in the skin or deep soft tissues. The neoplasm is composed of nodules of spindle-shaped endothelial cells forming slit-like spaces and epithelioid nodules of pericytes containing fibrin thrombi. Areas of fibrosis and abnormal lymphatic spaces may be seen at the periphery of the lesion.[96] While KHE has recently been reported within a CHE,[60] no histologic evidence of KHE was identified in our patient’s neoplasm.

Table 4:

Summary of reported primary intracranial kaposiform hemangioendothelioma.

CONCLUSION

We present the clinicopathologic features of a primary intracranial CHE in an adult man. The large hemorrhagic mass appeared to originate from the falx cerebri and infiltrate the overlying calvarium. Histopathologic examination of the resected neoplasm revealed a mixture of EHE, RHE, and hemangioma. Primary intracranial CHE has not been previously reported in the literature. Based on a review of published composite hemangioendotheliomas elsewhere in the body, this neoplasm should be managed with aggressive surgical resection when possible.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the Research Committee of University of Helsinki and with the 1964 Declaration of Helsinki and its amendments or comparable ethical standards.

Declaration of patient consent

Patient’s consent was not required as as patient’s identity is not disclosed or compromised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

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