November 2020, VOLUME 215

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November 2020, Volume 215, Number 5

Multispecialty Articles


A Review of the Spectrum of Imaging Manifestations of Epithelioid Hemangioendothelioma

+ Affiliations:
1Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215.

2Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

3Department of Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

4Department of Radiology, Beth Israel Lahey Health, Lahey Health Medical Center, Tufts University School of Medicine, Burlington, MA.

Citation: American Journal of Roentgenology. 2020;215: 1290-1298. 10.2214/AJR.20.22876

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OBJECTIVE. The purpose of this article is to review the spectrum of imaging manifestations of epithelioid hemangioendothelioma across different organ systems and briefly describe its current treatment strategies.

CONCLUSION. Epithelioid hemangioendothelioma is a rare, locally invasive neoplasm with metastatic potential. Although most commonly occurring in liver, lungs, and bones, it can also present at multiple other sites. Because of its nonspecific clinical and imaging manifestations, it is often misdiagnosed. The possibility of epithelioid hemangioendothelioma must be considered in the presence of a slowly growing mass that invades adjacent structures. Imaging can help plan percutaneous biopsy, detect sites of disease, and identify poor prognostic factors.

Keywords: epithelioid hemangioendothelioma, imaging, oncology, radiology, treatment

Epithelioid hemangioendothelioma (EHE) is a locally aggressive vascular neoplasm originating from vascular endothelial or preendothelial cells. It can arise anywhere in the body and can metastasize to the viscera, bones, and soft tissue. Dail and Liebow [1] first described this neoplasm in 1975 as an intravascular bronchoalveolar tumor involving the lungs. However, in 1982 the term “epithelioid hemangioendothelioma” was coined by Weiss and Enzinger [2] to denote a tumor composed of rounded or slightly spindled eosinophilic endothelial cells that grows in small nests or cords. The current classifications of the World Health Organization and the International Society for the Study of Vascular Anomalies characterize EHE as a locally aggressive vascular tumor with meta-static potential [35].

EHE has a prevalence of less than one case in 1 million individuals and accounts for approximately less than 1% of all vascular tumors. The mean patient age at presentation is 43 years, with a slightly higher preponderance of the neoplasm observed among female patients (1.6 female patients to 1 male patient) [3, 68]. The most common sites of involvement are the liver (21% of patients), bone (14%), and lung (12%) [3, 6]. However, EHE has been reported to involve many other sites throughout the body [914]. When the tumor is seen in multiple sites simultaneously, it is difficult to determine whether the lesions represent metastases from a single site or whether they represent multicentric tumors.

There are no definite known causative factors for EHE. Tanas et al. [15] identified WWTR1 (the WW domain–containing transcription regulator 1 gene) (3q25) and CAMTA1 (the calmodulin-binding transcription activator 1 gene) (1p36) as the two genes involved in the t(1;3)(p36;q25) chromosomal translocation that is seen in virtually all cases of EHE. However, Antonescu et al. [16] described a distinct subset of EHE that shows a YAP1-TFE3 gene fusion. This EHE subset is seen in adults who are slightly younger than other patients with EHE (mean age, 30 years) and does not show sex predilection. It has been suggested that chronic Bartonella infection could develop and induce intraerythrocytic and intraendothelial infections that might be associated with development of vascular tumors like EHE [17].

The clinical presentation of EHE is nonspecific and usually consists of signs and symptoms related to involvement of local organs by the primary tumor or metastases. Bone marrow involvement may manifest as consumption coagulopathy or hemolytic anemia [2, 18]. Approximately 28% of patients with EHE have no symptoms, and their tumor is discovered incidentally [6]. Because both clinical and imaging findings are nonspecific, establishing a diagnosis requires tissue sampling [2]. The appearance of EHE on microscopy is characterized by the presence of small nests or short cords of rounded to slightly spindled endothelial cells embedded in a myxoid hyalinized matrix. Compared with hemangiomas or well-differentiated angiosarcomas, the vascular differentiation is poorly developed with scattered small vascular channels. The most striking feature on microscopy is the presence of vacuolization of the cytoplasm, which is believed to represent primitive lumen formation [2, 3, 7]. A combination of the immunohistochemical markers Fli-1 and CD31 has been said to be ideal in characterizing the tissue as a vascular tumor [3, 19].

Because of the rarity of EHE and its diverse presentations, the existing literature on its imaging features is isolated to individual organs. Although previous articles have described the clinical and treatment considerations for EHE, our review details the spectrum of imaging manifestations of EHE across different organ systems and briefly discusses current strategies for its treatment.

Imaging Features
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Hepatic Epithelioid Hemangioendothelioma

The liver is the most common site of involvement of EHE. The imaging findings of hepatic EHE vary according to the stage of the disease, and two patterns have been reported: a nodular pattern, which is seen in the early stage of hepatic EHE and is characterized by discrete nodules ranging from 0.5 to 10.0 cm, and a diffuse pattern, which typically is seen in advanced stages and is characterized by lesions appearing as complex confluent coalescent masses that can be associated with hepatic vascular invasion. Lesions are commonly multifocal, are distributed in the periphery of the liver, and may be accompanied by capsular retraction [8, 2023].

On ultrasound, the nodular type of hepatic EHE is usually seen as hypoechoic nodules relative to the unaffected liver [20, 21]. In one study, 75% of lesions were hypoechoic on ultrasound, and the rest were either hyperechoic or of mixed echogenicity [24].

On unenhanced CT, lesions are isoattenuated or hypoattenuated to the liver parenchyma. Small foci of dense calcification may be present. The enhancement characteristics are variable (although most lesions show peripheral enhancement in the arterial phase and much stronger enhancement in the portal venous and delayed phases) and manifest as a target sign. Lesions may become isoattenuated to the liver parenchyma on the portal venous phase, in which case their extent may be more accurately determined on the unenhanced study. In a study by Miller et al. [24], 69% of EHEs showed peripheral enhancement, and in 77% of cases, lesion conspicuity on unenhanced images was as good or better than that on contrast-enhanced images. Therefore, in patients with suspected meta-static EHE, it may be useful to obtain unenhanced CT scans of the liver in addition to contrast-enhanced scans. In cases of extensive diffuse hepatic involvement, there may be volume loss with compensatory hypertrophy of the uninvolved portions of the liver, presumably because of vascular occlusion by tumor cells [21, 22, 24, 25].

On MRI, most EHE lesions are T1 hypoin-tense and heterogeneously T2 hyperintense relative to uninvolved liver parenchyma. Some lesions may have a concentric zonal or targetoid appearance on T2-weighted and contrast-enhanced T1-weighted images. The central low T2 signal intensity and reduced enhancement after contrast administration correspond to areas of avascular stroma, hemorrhage, necrosis, and calcification; peripheral high signal intensity and increased enhancement correspond to edematous connective tissue and viable tumor. This has been described as the black targetlike sign (Fig. 1). Less commonly, a central T2-hyperintense, enhancing, or nonenhancing core may be surrounded by a thin T2-hypoin-tense halo, in which case it is referred to as the white targetlike sign (Fig. 2). The pathologic significance of the white targetlike sign is unknown. In some cases, central necrosis may lead to a T2-hyperintense center, and in other cases there may be delayed enhancement of a fibrovascular core of the tumor [22, 2427]. The periphery of the tumor often shows markedly increased signal intensity on DWI, representing hypercellular tumor, whereas central regions show decreased signal intensity on high-b-value images as a result of relatively hypocellular, myxoid, and fibrous stroma [21, 22, 2527].

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Fig. 1A —46-year-old man who had undergone liver transplant for epithelioid hemangioendothelioma and was known to have biopsy-proven recurrent hepatic epithelioid hemangioendothelioma.

A, Axial T2-weighted MR image reveals mass in segment VIII of liver that shows peripheral T2-hyperintense and central intermediate-to-low T2 signal intensity (arrow), indicating black targetlike sign.

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Fig. 1B —46-year-old man who had undergone liver transplant for epithelioid hemangioendothelioma and was known to have biopsy-proven recurrent hepatic epithelioid hemangioendothelioma.

B, Coronal contrast-enhanced T1-weighted MR image shows peripheral rim enhancement (arrow).

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Fig. 2A —51-year-old man with metastatic epithelioid hemangioendothelioma who was receiving treatment with carboplatin.

A, Axial T2-weighted MR image shows mass in segment V that has central T2-hyperintense signal and faint peripheral T2-hypointense signal intensity (arrow) indicating white targetlike sign.

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Fig. 2B —51-year-old man with metastatic epithelioid hemangioendothelioma who was receiving treatment with carboplatin.

B, Axial DW image shows increased signal within mass (arrow).

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Fig. 2C —51-year-old man with metastatic epithelioid hemangioendothelioma who was receiving treatment with carboplatin.

C, Axial contrast-enhanced T1-weighted MR image shows homogeneous nodular enhancement of mass (arrow).

Thoracic Epithelioid Hemangioendothelioma

Thoracic involvement by EHE has been divided into four imaging patterns: a multinodular pattern, a reticulonodular pattern, a parenchymal tumor with pleural invasion, and diffuse pleural thickening [6, 7, 2830].

The multinodular pattern is the most common pattern and is associated with the best prognosis (Fig. 3). It is characterized by multiple discrete nodules, predominantly seen in a peribronchovascular distribution [29, 31]. The nodules are usually subcentimeter but might range from punctuate to 2 cm in size [32, 33]. This presentation of multiple bilateral pulmonary nodules can easily be misinterpreted as hematogenous pulmonary metastases or fungal granulomas. However, because of the indolent nature of the disease, little or no growth is observed on serial examinations [7, 34]. Tumor calcifications or cavitation is rare.

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Fig. 3 —63-year-old woman who had pulmonary epithelioid hemangioendothelioma with multinodular pattern and was receiving treatment with carboplatin and bevacizumab. Axial chest CT scan shows multiple nodules and mass lesions in both lungs, with several showing central calcification. Arrows point to representative lesions.

The reticulonodular pattern is characterized by multiple reticulonodular opacities associated with interlobular septal thickening and ground-glass opacities, mimicking hematolymphangitic metastases or diffuse interstitial lung disease [30, 31] (Fig. 4). Histopathologically, these reticulonodular opacities and interlobular septal thickening are attributed to infiltrating nodular proliferation of neoplastic cells within the lumens of small blood vessels and lymphatic vessels [29, 30].

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Fig. 4 —41-year-old woman with extensive pulmonary epithelioid hemangioendothelioma with reticulonodular pattern. Axial chest CT scan shows diffuse septal thickening in both lungs with scattered nodular and consolidative lesions representing metastatic epithelioid hemangioendothelioma. Arrows point to representative lesions.

The parenchymal tumor with pleural invasion is less common and is associated with the worst prognosis. This may be seen as a solitary lung mass or as multiple nodules with one or more dominant nodules that invade the adjacent pleura (Fig. 5). Pleural involvement is seen as enhancing pleural thickening or an enhancing pleural mass immediately adjacent to the parenchymal mass, often with associated pleural effusion [2931]. In some cases, FDG PET is helpful in identifying the pleural involvement that shows increased FDG uptake [29, 31].

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Fig. 5A —40-year-old woman with nonresectable right lung parenchymal epithelioid hemangioendothelioma with pleural and chest wall invasion; radiation therapy was planned.

A, Axial contrast-enhanced chest CT scan shows infiltrative mass that involves anterior subpleural aspect of right upper lobe, adjacent right upper pleura, right side of superior mediastinum, and right anterior chest wall (arrows). Note loculated right pleural effusion (P) with enhancement of right pleura indicating diffuse pleural involvement.

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Fig. 5B —40-year-old woman with nonresectable right lung parenchymal epithelioid hemangioendothelioma with pleural and chest wall invasion; radiation therapy was planned.

B, Coronal reformatted CT scan also shows destruction of medial aspect of right clavicle and obliteration of right brachiocephalic vein (arrows).

The diffuse pleural thickening pattern is uncommon and is seen as smooth or nodular thickening of the pleura, which can extend into the fissures and is often associated with pleural effusion. This pattern is most commonly confused with pleural mesothelioma or pleural metastases [2831]. Although involvement of the adjacent lung parenchyma is often seen, there may also be extension into the chest wall [2931].

Osseous Epithelioid Hemangioendothelioma

In the musculoskeletal system, the order of frequency of involvement is as follows: the long bones of the lower extremity, the long bones of the upper extremity, the axial skeleton (calvaria, scapulae, pelvic bones, and vertebrae), the clavicles, and the ribs. The most frequently affected long bones are the tibia (23%), femur (18%), and humerus (13%) either proximally or distally [18, 35, 36]. When EHE involves the soft tissues, it tends to occur along the vessels [35, 36]. Involvement of the verte-brae is rare, and EHE does not appear to have a propensity to involve specific regions of the spine on the basis of existing literature [37].

Radiography and CT typically show multifocal poorly demarcated osteolytic lesions involving both the medullary cavity and the cortex near the ends of the bone. There is surrounding sclerosis and no matrix mineralization. Cortical disruption and extension into the surrounding soft tissues can be present. Periosteal reaction is rare and is seen in the setting of pathologic fractures. Adjacent joint invasion is a common feature [18, 35, 38]. CT shows features similar to those seen on radiography, although the extent of bony involvement can be better shown. On contrast-enhanced images, the lesions show homogeneous enhancement [3739].

Although there is no representative pattern of signal intensity on MRI, bone EHE has low-to-intermediate signal intensity on T1-weighted unenhanced images and high signal intensity on T2-weighted images, with homogeneous enhancement after IV contrast injection (Fig. 6). Soft-tissue extension is best seen on MRI [3, 18, 35]. Likewise, MRI is essential to characterize epidural extension and involvement of neurologic structures in cases of EHE of the spine [32, 33, 37].

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Fig. 6A —57-year-old woman with slowly enlarging bulge in left side of head, which was diagnosed as epithelioid hemangioendothelioma of left frontal bone.

A, Axial MR images show mass in left frontal bone with intermediate T1 signal intensity (arrow, A) and T2 hyperintensity (arrow, B) and with homogeneous enhancement observed after administration of contrast medium (arrow, C). Note extension into adjacent soft tissue of scalp (arrowhead).

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Fig. 6B —57-year-old woman with slowly enlarging bulge in left side of head, which was diagnosed as epithelioid hemangioendothelioma of left frontal bone.

B, Axial MR images show mass in left frontal bone with intermediate T1 signal intensity (arrow, A) and T2 hyperintensity (arrow, B) and with homogeneous enhancement observed after administration of contrast medium (arrow, C). Note extension into adjacent soft tissue of scalp (arrowhead).

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Fig. 6C —57-year-old woman with slowly enlarging bulge in left side of head, which was diagnosed as epithelioid hemangioendothelioma of left frontal bone.

C, Axial MR images show mass in left frontal bone with intermediate T1 signal intensity (arrow, A) and T2 hyperintensity (arrow, B) and with homogeneous enhancement observed after administration of contrast medium (arrow, C). Note extension into adjacent soft tissue of scalp (arrowhead).

EHE shows increased uptake on 99mTc sestamibi bone scintigraphy. Because of its multicentric nature, bone scanning can be helpful for evaluation of the extent of the disease [18, 40, 41]. Serial bone scintigraphy has been used to monitor response [42]

Other Sites

EHE can involve multiple sites in the body, although these are rare compared with hepatic, thoracic, and musculoskeletal involvement. Intracranial primary EHE is rare, and both intraaxial and extraaxial tumors have been described, although some of these may not meet the current pathologic criteria for EHE [11, 43]. In the neck region, EHE has been described as involving the larynx, the gingiva, the eyelid, the submandibular region, the nasal cavity, and the tongue [10, 44]. In the thorax, in addition to pulmonary and pleural involvement, EHE has also been reported to originate primarily in the mediastinum [45] (Fig. 7). In the abdomen, in addition to hepatic involvement, EHE is known to occur in the stomach, small bowel, large bowel, peritoneum, and retroperitoneum [13, 4650]. In the genitourinary system, EHE is known to involve the uterus, ovary, vulva, clitoris, prostate, penis, and testis [12, 5154]. Other rare sites of primary EHE include the lymph nodes, breast, and intravascular origin [14, 5557].

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Fig. 7A —24-year-old man with shortness of breath.

A, Axial CT scan of chest shows anterior mediastinal mass (arrow) with foci of calcifications (white arrowhead) and low-attenuation areas (black arrowhead), which initially were thought to represent teratoma.

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Fig. 7B —24-year-old man with shortness of breath.

B, Axial fused FDG PET/CT image shows intense uptake within mass (arrow). Percutaneous biopsy revealed epithelioid hemangioendothelioma.

There often is a delay in diagnosing EHE at these unusual sites because its nonspecific clinical presentation and rarity make it less likely for clinicians to consider EHE in their differential diagnosis (Fig. 8). Imaging usually shows an ill-defined soft-tissue mass that shows mild enhancement. There may be evidence of invasion of the adjacent structures. Comparison with prior imaging can show the slow growth rate that is usually seen with EHE relative to that seen with other neoplasms [3].

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Fig. 8A —38-year-old woman with swelling in right anterior thigh.

A, Gray-scale ultrasound images of mid right femoral vein without (left, A) and with compression (right, A) and color Doppler ultrasound image of right proximal femoral vein (B) show hypoechoic filling defect in right vein (arrows). This was thought to be thrombus, and patient was treated with anticoagulative agents. However, because there was no change after 4 weeks of treatment, MRI was performed.

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Fig. 8B —38-year-old woman with swelling in right anterior thigh.

B, Gray-scale ultrasound images of mid right femoral vein without (left, A) and with compression (right, A) and color Doppler ultrasound image of right proximal femoral vein (B) show hypoechoic filling defect in right vein (arrows). This was thought to be thrombus, and patient was treated with anticoagulative agents. However, because there was no change after 4 weeks of treatment, MRI was performed.

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Fig. 8C —38-year-old woman with swelling in right anterior thigh.

C, Axial contrast-enhanced T1-weighted subtracted MR image shows heterogeneously enhancing mass in right femoral vein (arrow). Biopsy showed epithelioid hemangioendothelioma.

Role of PET/CT

Fluorine-18FDG PET is not routinely used for the diagnosis of EHE because FDG uptake is variable. In one study, two-thirds of hepatic EHEs showed increased FDG uptake, and one-third showed uptake similar to that in the liver [58]. FDG PET may be used to evaluate for multicentric EHEs and to detect metastases [59] (Fig. 9). When EHE presents as multiple pulmonary nodules, it has been reported that increased FDG uptake may correspond to a higher grade of malignancy, and FDG uptake can therefore be used to target lesions for surgical resection [60, 61].

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Fig. 9A —55-year-old woman who presented with chest pain and underwent MRI to further characterize masslike lesion seen in aorta on initial CT examination.

A, Sagittal MR angiogram of chest shows irregular mass in posterior wall of proximal descending thoracic aorta (arrow).

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Fig. 9B —55-year-old woman who presented with chest pain and underwent MRI to further characterize masslike lesion seen in aorta on initial CT examination.

B, Axial double-inversion recovery contrast-enhanced T1-weighted MR image mass shows heterogeneous enhancement (arrows).

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Fig. 9C —55-year-old woman who presented with chest pain and underwent MRI to further characterize masslike lesion seen in aorta on initial CT examination.

C, Coronal maximum-intensity-projection FDG PET image shows multiple foci of uptake, including thoracic spine (white arrowhead), descending thoracic aorta (white arrow), right iliac bone (black arrow), and right femur (black arrowhead). Biopsy of lytic lesion in right iliac bone showed metastatic epithelioid hemangioendothelioma.

A subset of EHE expresses somatostatin receptor [62]. In this group, 68Ga-DOTA-DPhel-Tyr3-octreotate (DOTATATE) PET/CT can help to detect metastases and measure tumor burden, and it can also be used for targeted radionuclide therapy [63].

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The natural course of EHE is variable depending on the primary site of involvement, grade of the tumor, presence of invasion of critical structures, and presence of metastases. EHE has a wide range of malignant potential, and although some tumors progress rapidly and lead to death within a few years of diagnosis, some may even show spontaneous regression [6, 7]. In a study by Lau et al. [6], the overall survival rate for patients with EHE was 90% at 1 year and 73% at 5 years, with a lower survival rate noted among male patients and patients 55 years old or older. In the study by Lau et al., there was no difference in survival among patients with single or multiple organ involvement. However, diffuse pulmonary infiltrates, extrapulmonary thoracic disease, pleural effusion, peritoneal tumor deposits, ascites, and involvement of three or more bones were associated with worse prognosis. Presence of symptoms is associated with a worse prognosis. Although the mean survival of patients with pulmonary EHE is 4.6 years (range, 6 months to 24 years), patients with asymptomatic pulmonary EHE have a longer median survival (180 months) [3, 6, 64]. In a study by Bagan et al. [64], the presence of alveolar hemorrhage, hemoptysis, hemorrhagic pleural effusion, and anemia was associated with worse prognosis (overall survival, < 1 year). Histologic findings of spindle tumor cells and higher mitotic activity (more than three mitotic figures per 50 high-power fields) show worse prognosis [3, 7, 64, 65]. Most patients die of respiratory failure as a result of progressive lung parenchymal replacement. A small proportion of patients die of extensive hepatic or bone metastases [3, 6, 64].

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Because the presentation, natural course, and prognosis of EHE are widely variable, there is no single standard treatment option, and the need for and type of therapy must be individualized for each patient. An initial period of observation with interval scanning is often recommended for patients with no symptoms or those with other serious comorbidities precluding treatment. In such patients, repeat imaging and clinical evaluation are conducted to assess the clinical behavior, and if there is evidence of progression, prompt treatment should be considered [66]. When the lesions are small and limited in number, surgical resection is recommended and may be curative [3].

Liver transplant can be curative for patients with hepatic EHE for whom complete surgical resection is not feasible. The presence of limited extrahepatic extension is not a contraindication for liver transplant [6769]. Recurrent hepatic EHE is seen in approximately 25% of patients after liver transplant. Macrovascular invasion, a pre-transplant waiting time of 120 days or less, and hilar lymph node invasion are significant risk factors for recurrence [70].

For patients with unilateral single or multiple EHE lung nodules, wedge resection is recommended and offers the same outcome as wider anatomic resection. Because of the low number of patients with lymph nodal metastases, there are insufficient data on the outcomes after hilar and mediastinal lymph node resection [3, 64]. Management of pleural disease and multiple nodules is challenging because complete surgical resection is often not feasible.

En bloc resection is used for solitary osseous lesions, and when necessary amputation is used for multicentric lesions. For patients with pathologic fracture, temporary stabilization may be needed before definite surgery. Radiofrequency ablation has been used before surgery to decrease the extent of resection and symptomatic pain management [71, 72].

Radiation therapy does not have a significant role in the management of EHE because of the slow growth rate of the neoplasm and its low sensitivity to radiation. However, radiation therapy has been used to control residual disease after incomplete resection, particularly in patients with osseous EHE [3, 32].

Patients with slowly progressing EHE may benefit from treatment with celecoxib because of its antiangiogenic properties. For more rapidly progressing forms of EHE, a treatment approach similar to that used for angiosarcoma has been tried, with carboplatin, paclitaxel, anthracyclines, and ifosfamide offering modest benefits [66, 73]. However, there is no concrete evidence of survival benefit from conventional chemotherapy [73, 74]. Antiangiogenic drugs, which target vascular endothelial growth factor receptor, have been used because expression of vascular endothelial growth factor receptor has been shown in EHE. Few studies have shown a partial response of EHE tumors to the combination of conventional chemotherapy and antiangiogenic therapy in the form of carboplatin, paclitaxel, and bevacizumab [66, 75]. The PI3K-Akt-mTOR (phosphatidylinositol-3-kinase–protein kinase B–mammalian target of rapamycin) pathway has been identified as having an important role in sarcomagenesis for both EHE and angiosarcoma. More recently, sirolimus, which is a drug targeting the mammalian target of rapamycin pathway, has been used for the treatment of EHE. Among patients treated with sirolimus as a single agent, clinical benefit was noticed in 56% [76]. Immune checkpoint inhibitors are being explored for the treatment of sarcomas and may play a role in the treatment of EHE in the future [77, 78]. All are meant to denote genes. Future targeted therapeutic strategies may be developed to target the WWTR1-CAMTA1 or YAP1-TFE3 mutations, which are known to occur with EHE [15, 16].

Role of Imaging
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Although there are no definitive imaging features of EHE, radiologists can raise this possibility for tumors that show slow growth across scans relative to that of other tumors, despite invasion of local structures. Because establishing a definite diagnosis requires biopsy, imaging can help determine the safest approach for obtaining a tissue sample. Imaging can provide critical prognostic information by identifying sites of metastases, the pattern of pulmonary disease, pleural ef-fusion, and ascites. Imaging is essential to monitor treatment response. Antiangiogenic agents are increasingly being used to treat EHE, and radiologists must promptly identify their associated toxicities, such as thromboembolic events and end-organ damage caused by hypertension, including posterior reversible encephalopathy syndrome, tumor-organ fistula, and pancreatic atrophy [79].

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EHE is a rare, locally aggressive vascular tumor with metastatic potential that can originate anywhere in the body but frequently involves the liver, lungs, and bones. Although imaging features are nonspecific, the possibility of EHE must be considered in cases of slowly growing tumors in the classic sites that invade adjacent organs as well as in peripherally enhancing hepatic lesions with a targetoid appearance. EHE shows variable clinical and biologic behavior, and the treatment strategy should be tailored to the individual patient and toward alleviating symptoms. Imaging plays an important role in determining sites of involvement, which has important prognostic significance. Imaging can also help to guide biopsy and local therapy and to monitor response to treatment.

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