Abstract
Intravascular papillary endothelial hyperplasia is a rare benign vascular proliferative process as a result of papillary proliferation of the endothelial cells within the vascular lumen. We report two cases of intravascular papillary endothelial hyperplasia affecting the extremities. The characteristic sonological and MR imaging features are discussed, with updated review of literature. Imaging features are helpful in achieving a definitive diagnosis of the intravascular papillary endothelial hyperplasia.
As per the name, an intravascular papillary endothelial hyperplasia (IPEH) is a reactive proliferative lesion of endothelial cells within the vessels, initially described in 1923 by Masson, is also known as Masson's tumor, intravascular angiomatosis, and vegetant intravascular hemangioendothelioma. Microscopically, the lesion has the appearance of numerous small papillary structures covered by a single layer of flattened endothelium around cores of fibrous connective tissue. Thrombi in various stages of organization are almost always detected (1, 2).
Intravascular papillary endothelial hyperplasia is usually classified into three forms according to Hashimoto et al. (3), a primary or pure form that arises in dilated vascular spaces; a mixed form that occurs in pre-existing vascular abnormalities, such as hemangioma, arteriovenous malformations; and a rare extravascular form that arises in hematoma.
Case reports
Case 1
A 39-year-old woman complained of acute, non-painful swelling behind the left knee joint since 1.5 months. On examination there was 2 cm palpable mobile, non-tender, non-compressible, and non-pulsatile mass at the posterior aspect of the left knee joint. There was no definite history of trauma. On ultrasound, the mass was 25 mm long and 10 mm wide with a heterogeneously hypoechoic mass at the posterior aspect of left knee joint (Fig. 1a). There was septal and central vascularity on power Doppler (Fig. 1b). MRI showed a T1W hypointense mass containing two hyperintense nodular foci. On T2W image, the mass was hyperintense with multiple low signal intensity nodules (Fig. 2a). Post gadolinium contrast examination showed peripheral, septal, and central enhancement (Fig. 2b).
A 39-year-old woman complained of acute, non-painful swelling behind the left knee joint since 1.5 months. (a) Grey-scale ultrasound of the left knee showing 25 mm long × 10 mm wide mass at the posterior aspect superficial to muscles – note hypoechoic nodular foci (white arrowheads) with echogenic septae (white arrows) and center (black arrowhead); (b) Color Doppler US shows septal vascularity
(a) Coronal T2-weighted image shows the subcutaneous hyperintense mass with multiple foci of low signal intensity (white arrows); (b) Axial gadolinium-enhanced T1-weighted images reveal peripheral (black arrow), septal (white arrow), and central enhancement (arrowhead)
Case 2
A 28-year-old man presented with non-traumatic sizable swelling over the left ankle. On examination, this mobile mass was 3 cm in size. On ultrasound, an elongated hypoechoic mass was identified on the lateral aspect of the left ankle (Fig. 3). The mass was 28 mm long, 35 mm deep, and 26 mm wide and showed septal vascularity on color Doppler. Valvular incompetence was demonstrated in the left common femoral vein and the upper superficial femoral vein. Further MRI showed T1W a hypointense mass containing nodular foci of high signal intensity. These foci were low intense signal on T2W images. Similar to the first case, a peripheral, septal, and central enhancement was identified on post gadolinium T1W images (Fig. 4).
A 28-year-old man presented with non-traumatic sizable swelling over the left ankle. Grey-scale ultrasound of the left ankle showing 18 mm long ×7 mm deep ×20 mm wide elongated mass. Note hypoechoic mass (black arrow) with echogenic septa (white arrows)
Sagittal gadolinium-enhanced T1-weighted images reveal peripheral (white arrow), septal (black arrow), and central enhancement (arrowhead)
These imaging features were compatible with intravascular papillary endothelial hyperplasia. Ultrasound-guided biopsy was done in the first case, which showed a thrombus with growing endothelial cells. The septae and central area contained small vessels, which well correlated with the enhancing or vascularized portions on the MRI and US.
Both cases were treated conservatively with an uneventful clinical course.
Discussion
Though not specific, location of IPEH is associated with definite varying demographic features according to its subtype (4). Most common site for primary form is the subcutis layer of the extremities, followed by the head and neck, and elbow to hand. The mixed-form lesions do not show a preferred site, however 50% of lesions are reported intramuscularly (4). It has a varied range of occurrence ranging from 9 months to 78 years with slight preponderance on women over men (3). The pure form (average 1.75 cm in size) is smaller than the extra-vascular form (average 4.5 cm in size) (5). The lesion is usually solitary but may occasionally be multiple. An antecedent history of trauma has been reported in 4% of the patients (6).
The pathogenesis of IPEH is presumably related to an unusual form of thrombus organization. The exuberant endothelial cell proliferation may be stimulated by an autocrine loop of endothelial basic fibroblast growth factor (bFGF) secretion. The proposed mechanism is that IPEH development is triggered by the release of bFGF from macrophages attracted to a site of trauma. The proliferating endothelial cells release more bFGF, setting up a positive feedback loop of endothelial proliferation (7).
There are few reports in the literature describing the imaging features of IPEHs occurring in the extremities: four describe MRI features (4, 8–10) and two describe US features (11, 12). The US findings of IPEH arising in an extremity, which was a pure type of IPEH occurring in a wrist, was hypoechoic compared with subcutaneous fat and was confirmed to be arising from the vein after tourniquet application to distend the affected vein (12). In another case study, US was performed in three IPEHs. One pure form that arose in a finger was also homogeneously hypoechoic compared with subcutaneous fat with septal and peripheral vascularities on color Doppler imaging; however, venous distension images using tourniquet application were not obtained. The other two mixed forms of IPEH showed well-defined hypoechoic masses containing hyperechoic septa and central portion with vascularities.
The previous MRI findings were described differently, and the features appeared to be variable. However, in a recently published study, which includes the largest number of patients so far, SJ Lee et al. (11) have described the MR imaging features in six histologically confirmed IPEH. The imaging features of the mixed form are diagnostic while those of the pure form are non-specific. On MRI, the mixed form of IPEH that occur in extremities is a well-defined mass with T2 hyperintense signal containing nodule-like foci of low signal intensity, T1 iso- to slightly hyperintense signal containing nodule-like foci of high signal intensity, and peripheral/septal or central enhancement. On ultrasound it is a hypoechoic mass containing hyperechoic septae. The septal vascularities can be demonstrable on color Doppler. The imaging findings of the pure form of IPEH are non-specific. Similar imaging features were identified in both the patients.
In other reports, the MR imaging appearances of the IPEH of the extremities (6, 8) usually showed intermediate or slightly high-intensity signal on T1W images, and heterogeneously high-intensity signal on T2W images, correlating with the different stages of thrombus formation. Corti et al. (13) mentioned changes in the signal intensity of the thrombi from the acute stage to the intermediate stage (from the first to the third week). The signal intensity of the thrombi is higher during the first week and then decreases progressively. Juan et al. (9) suggested that the MR characteristics of a soft-tissue mass accompanied by areas of hemorrhage and nodule-like low signal reflecting organized thrombi should allow the differentiation of IPEH from other neoplasm. Due to the heterogeneity, resulting from the mixture of the solid cellular elements, hemorrhage, and the fibrous collagenized region, the radiological appearance of IPEH may mimic malignant soft tissue tumors such as synovial sarcoma (14). However, in contrast to intra-tumoral hemorrhages, the areas of thrombi in IPEH tend to be arranged regularly. In addition, IPEH tend to show septal and/or central enhancement surrounding the thrombi in contrary to malignant tumors, which usually show a random heterogeneous enhancement, helping in the definitive differentiation between IPEH and malignant tumor. Though rare, owing to pleomorphism or mitotic atypia, IPEH may resemble an angiosarcoma on histology (15). However, intravascular location of IPEH may help to differentiate it from angiosarcoma which is rarely confined within the vascular lumen.
The treatment of choice for IPEH is complete surgical excision because the masses do not usually spontaneously resolve. Recurrence may occur if the lesion is not completely excised (10). Recurrence rate is about 10% and is more common in the mixed form.
In conclusion, IPEH is a rare benign disease with classical imaging features of a mixed IPEH variety. These cases add evidence to previously described imaging features which help in facilitating the early diagnosis and obviating the need of an invasive procedure in many circumstances.