Cerebral Intricacies: Deciphering the Mystique of Primary Central Nervous System Angiosarcoma

Abstract

Angiosarcoma of the central nervous system (CNS) is an exceptionally rare and aggressive vascular malignancy presenting significant diagnostic and therapeutic challenges. We report the case of a 22-year-old female with CNS angiosarcoma, highlighting diagnostic intricacies, therapeutic approaches, and management outcomes. Initial symptoms included headache and dizziness, with magnetic resonance imaging revealing a space-occupying lesion in the right parietal lobe, initially misinterpreted as cavernoma. Subsequent surgical resection confirmed angiosarcoma histologically, supported by immunohistochemical analysis showing endothelial markers. Treatment comprised local irradiation postoperatively, resulting in no recurrence or metastasis. Histopathological examination revealed an infiltrative growth pattern with atypical endothelial cells forming irregular vascular spaces. Challenges in diagnosis arise due to overlapping features with other intracranial lesions. Multimodal treatment approaches involving surgery, radiation, and chemotherapy were employed, although their efficacy remains uncertain. Prognosis remains poor, underscoring the imperative for collaborative efforts to enhance understanding and management of this rare malignancy. Our case contributes valuable insights to the limited literature on CNS angiosarcoma, emphasizing the need for comprehensive case studies to refine diagnostic and therapeutic strategies.

 

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Keywords

cerebral - angiosarcoma - central nervous system - cavernoma - epithelioid

Introduction

Angiosarcoma of the central nervous system (CNS) is an exceedingly rare and highly aggressive vascular malignancy that arises from the endothelial cells of blood vessels within the brain and spinal cord. Although angiosarcomas commonly manifest in soft tissues, bones, and the skin, their occurrence within the CNS is a distinctive and challenging clinical entity.[1] [2] This case report delves into the diagnostic intricacies, therapeutic dilemmas, and the overall management of a patient diagnosed with angiosarcoma of the CNS.

The rarity of angiosarcoma in the CNS poses a considerable challenge for clinicians, as the clinical presentation, radiological features, and histopathological characteristics often mimic other, more common intracranial lesions. Limited literature is available regarding the natural history and optimal management strategies for CNS angiosarcomas, necessitating a comprehensive exploration of individual cases to understand this enigmatic disease better.

Through a meticulous examination of pertinent literature and the presentation of a specific case, this report aims to contribute to the growing body of knowledge surrounding CNS angiosarcomas. Insights gained from such cases are pivotal for refining diagnostic approaches, elucidating prognostic factors, and formulating effective therapeutic strategies. The discussion will address challenges in accurate diagnosis, the role of advanced imaging modalities, the intricacies of histopathological interpretation, and the evolving landscape of treatment options.

 

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Case Report

A 22-year-old female presented with headache and dizziness for 4 months with an insignificant past history. Initially, magnetic resonance imaging was advised, which revealed an intensely enhancing space-occupying region in the parafalcine region in the right parietal lobe measuring 9.6 × 8.3 × 9.3 cm ([Fig. 1A]). It was isointense on T1-weighted image with peripheral T1 hypointense rim, heterogeneously hyperintense center with the peripherally hypointense rim on T2 with significant blooming and surrounding perilesional edema. Based on the radiological findings, a possibility of cavernoma was suggested. A craniotomy was performed and a firm vascular tumor was removed and sent for histopathological examination.

Fig. 1 Magnetic resonance imaging (MRI) scans and histopathological findings. (A) MRI revealed an intensely enhancing space-occupying region in the parafalcine region in the right parietal lobe measuring 9.6 × 8.3 × 9.3 mm. (B, C) Hematoxylin and eosin-stained sections exhibited an infiltrative growth pattern characterized by densely packed, epithelioid cells along with the presence of irregular vascular channels lined by atypical endothelial cells (100× , 400×).

Microscopic examination revealed an infiltrative growth pattern characterized by densely packed, epithelioid cells invading the adjacent brain parenchyma. The cellular arrangement lacked architectural organization, with nests and cords of epithelioid cells dispersed within a fibrovascular stroma. These epithelioid cells exhibited pleomorphic features, including enlarged nuclei with prominent nucleoli, irregular nuclear contours, and eosinophilic cytoplasm.

A distinctive histological feature was the presence of irregular vascular channels lined by atypical endothelial cells interspersed throughout the tumor mass. These channels exhibited variable sizes and shapes, often showing a sinusoidal or slit-like appearance, and frequently contained erythrocytes ([Fig. 1B, C]). Immunohistochemical analysis demonstrated diffuse positivity for endothelial markers such as vimentin, CD31 (mouse monoclonal, clone BC2, Biocare Medical), epithelial membrane antigen (mouse monoclonal, clone E29, Biocare Medical), vascular endothelial growth factor (rabbit monoclonal, clone EP1176Y, Biocare Medical), and ETS-related gene (mouse monoclonal, clone 9FY, Biocare Medical), confirming the endothelial origin of the neoplastic cells. K_i-67 proliferation index (mouse monoclonal, clone MIB-1, Biocare Medical) was 35 to 40%. The tumor cells were negative for glial acidic fibrillary protein (mouse monoclonal, clone GA-5, Biocare Medical) and pan-cytokeratin (mouse monoclonal, clone AE1AE3–5D3, Biocare Medical) ([Fig. 2]).

Fig. 2 Histopathological and immunohistochemical panel for confirmation of diagnosis (A,B) Hematoxylin and eosin stained sections show an infiltrative tumor characterized by densely packed, epithelioid cells invading the adjacent brain parenchyma (C-H) Tumor cells exhibit positive expression for vimentin (C), epithelial membrane antigen (EMA) (D), CD31 (E), ETS-related gene (ERG) (F), vascular endothelial growth factor (VEGF) (G), and a Ki67 proliferation index of 30% (H) (100, 400).

Positron emission tomography scan was performed, and no extracranial tumor was identified. Further, there were no signs or symptoms suggestive of an extracranial tumor anywhere else. Based on the histopathological and radiological findings, a final diagnosis of primary cerebral angiosarcoma was made. Her postoperative period was uneventful without any complications. She was given a course of local irradiation delivering 20 Gy to the area of the lesion in the right parietal lobe. Postoperatively, she responded well with no evidence of recurrence or metastasis.

 

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Discussion

Angiosarcoma of the CNS remains an exceptionally rare neoplasm, posing diagnostic and therapeutic challenges for clinicians. The limited number of reported cases contributes to the scarcity of comprehensive studies, making each case crucial for expanding our understanding of this enigmatic entity. This discussion focuses on key aspects such as diagnostic difficulties, treatment modalities, and the prognosis associated with CNS angiosarcoma.

Accurate diagnosis of CNS angiosarcoma is intricate due to its rarity and overlapping clinical and radiological features with other more common intracranial lesions. The World Health Organization's classification of tumors of the CNS has provided a foundation for understanding the histopathological characteristics of CNS tumors.[1] However, distinguishing angiosarcoma from other vascular lesions and malignancies often requires an integrated approach involving advanced imaging techniques and molecular studies.

Histopathological examination remains the gold standard for diagnosis. The characteristic presence of atypical endothelial cells forming irregular vascular spaces, along with immunohistochemical markers such as CD31 and CD34, aids in confirming the diagnosis.[2] However, challenges persist, especially when faced with small biopsy specimens or overlapping histological features. Only a limited number of instances involving primary cerebral angiosarcoma have been documented, with epithelioid angiosarcomas being even rarer within this subset.[3] [4] [5] [6] [7] [8] [9] [10] [Table 1] summarizes the previously reported cases of primary cerebral angiosarcomas.

Table 1 Clinicopathological features of previously reported cases of cerebral angiosarcoma

Author	Age/Gender	Clinical presentation	Location	Radiological findings	Immunohistochemistry and diagnosis	Therapy	Outcome
Kuang et al[3] (2023)	73/M	Headache for 1 month	Right occipital lobe	MRI: A mass in the right occipital lobe, with low and high mixed signals on T1-weighted images	CD31+, ERG+, FL-1+, CK+ Epithelioid angiosarcoma	Surgery followed by radiotherapy	Death after 9 months
Hirai et al[4] (2023)	72/M	Progressive hemiparesis	Diffuse cerebrum and ventricle	MRI: Nodular shadow in the hematoma with a slightly enhancing margin but no enhanced nodules, including nonbleeding lesions	CD31+, ERG+ Angiosarcoma	Surgery followed by radiotherapy	Died 4 months after disease onset
Arafat et al[5] (2023)	50/F	Repetitive, rhythmic, uncontrolled movements associated with a loss of consciousness	Left frontal lobe	MRI: An enhancing left frontal intra-axial lesion with slight heterogeneity that is mainly hypointense on both T1 and T2, showing blooming artifact	CD31+, CD34+ (focal), FL-1+ Epithelioid angiosarcoma	Surgery followed by chemoradiation	Doing well, under follow-up
Valera-Melé et al[6] (2022)	41/M	Seizures and headache	Right frontal lobe	CT: Hyperdense right frontal lobe mass ([Fig. 1A]), suggesting a hemorrhagic tumor	Angiosarcoma	Surgery followed by chemoradiation	Relapse at 5 months followed by death
Gao et al[7] (2019)	68/M	Confusion and progressive impairment of right limb movement	Left frontal lobe	MRI: Hemorrhagic lesion in the left frontal lobe	Angiosarcoma	Surgery	Tumor recurrence at 1 month followed by death after 4 weeks
Jerjir et al[8] (2016)	61/M	Subacute, aggravating headaches	Left frontotemporal lobes	CT: 5.8 cm large and well-defined spontaneously hyperattenuating lesion in the left frontotemporal lobes	Angiosarcoma	Surgery followed by radiotherapy	Doing well, under follow-up
La Corte et al[9] (2015)	35/F	Weakness and sensory disturbances of her right hand	Left frontal posterior region	–	CD31 + , CD34+ Epithelioid angiosarcoma	Surgery followed by chemoradiation	Under follow-up
Hackney et al[10] (2012)	35/F	Exophthalmos with blurred vision	Left retro-orbital infratemporal area	CT: Homogeneous mass of the left retro-orbital infratemporal area compressing the temporal lobe and displacing the left optic nerve	CD31+ Epithelioid angiosarcoma	Surgery followed by radiotherapy and bevacizumab	Doing well, under follow-up

Abbreviations: CT, computed tomography; F, female; M, male; MRI, magnetic resonance imaging.

The optimal management of CNS angiosarcoma is not well defined, primarily due to the rarity of the disease. Treatment strategies often involve a multimodal approach, including surgery, radiation therapy, and systemic chemotherapy. However, the efficacy of these interventions remains uncertain, and there is a lack of standardized protocols.

Surgical resection is considered the primary treatment modality when feasible, aiming for maximal safe tumor removal. Given the infiltrative nature of angiosarcomas, achieving complete resection may be challenging, leading to a high recurrence rate. Adjuvant therapies, such as radiation and chemotherapy, are often employed to address residual disease or manage unresectable tumors. Studies suggest that doxorubicin-based chemotherapy regimens may offer some benefit, although responses can be variable.[11]

The prognosis for patients with CNS angiosarcoma is generally poor, with a high likelihood of recurrence and metastasis. The limited available data make it challenging to identify reliable prognostic factors. Factors such as age, extent of surgical resection, and response to adjuvant therapies may influence outcomes, but further research is necessary for a more nuanced understanding of prognostic indicators.

In conclusion, the rarity of epithelioid angiosarcoma in the CNS presents significant diagnostic and therapeutic challenges. Collaborative efforts across multiple institutions are essential to accumulate more cases and facilitate a better understanding of this uncommon malignancy. Continued research and the development of standardized treatment approaches are crucial to improving outcomes for patients with CNS angiosarcoma.

 

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Conflict of Interest

None declared.

Authors' Contributions

S.A., S.M., and C.A. contributed significantly to the project in various capacities. All three were involved in the concepts, design, data acquisition, and manuscript editing. S.A. also contributed to the definition of intellectual content, literature search, data analysis, manuscript preparation, and review. S.M. participated in data acquisition, design, and manuscript editing. C.A. contributed to data acquisition, data analysis, manuscript editing, review, and served as the guarantor for the project.

Ethical Approval

The study was done in accordance with the Declaration of Helsinki.

Patients' Consent

Informed consent was taken from the patient.

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Publication History

Article published online:
15 January 2025