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.
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. Ki-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.
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.
