Intravascular Papillary Endothelial Hyperplasia – Case Report

1 Department of Dermatology, Elias Emergency University Hospital, Bucharest, Romania 2 Department of Dermatology, „Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 3 Department of Pathology, Elias Emergency University Hospital, Bucharest, Romania 4 Department of Oncology, Elias Emergency University Hospital, Bucharest, Romania 5 Department of Oncology, „Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Corresponding author: Liliana Gabriela Popa, Department of Dermatology, Elias Emergency University Hospital, No. 17 Marasti Bd, Bucharest, Romania. E-mail: lilidiaconu@yahoo.com Abstract


Intravascular Papillary Endothelial Hyperplasia -Case Report INTRODUCTION
Intravascular papillary endothelial hyperplasia (IPEH), fi rst described by Pierre Masson in 1923 is an uncommon benign vascular lesion that involves the skin or the soft tissue 1 .IPEH represents 2-4% of vascular tumors arising in the skin and soft tissue 2 .It usually occurs in the fourth decade of life and has a slight predilection for the female gender 3 .cated in the lower left abdominal area that had appeared 12 months earlier.Th e patient denied any previous trauma in that region.Th e lesion was a well circumscribed, 2/1 cm, ovalar, bluish-purple, soft, non-pulsatile mass with an irregular surface.Th e overlying epidermis showed no changes (Figure 1).Th e patient complained of local tenderness on palpation.Th e general physical examination did not reveal other pathologic changes, except for the paleness of the skin and mucous membranes.Th e patient suff ered from chronic moderate hyposideremic anemia, for which gastrointestinal and gynecologic causes had been excluded.She was under specifi c treatment prescribed by the haematologist.
Th e results of the laboratory tests were within normal limits, except for the moderate hyposideremic anemia.
Th e ultrasound examination showed an encapsulated 2.2/0.8cm hypoechogenic mass located in the skin and subcutaneous tissue, suprajacent to the muscular fascia.Doppler evaluation showed peripheral vascularization, with minimal arterial and venous fl ows.
Th e lesion was surgically excised under local anesthesia.Th e histopathologic examination revealed a dermal tumor, partially delineated by fi bro-hialine fascicles of variable thickness (a pseudocapsule), with multiple pseudocystic spaces of various dimensions occupied by erythrocytes and a homogenous eosinophilic material, that contain papillary structures lined by a single layer of fl at/cubic epithelium surrounding a collagenized core (Figure 2).In several sites, the papillary projections fuse to form a network of anastomosing vessels.Immunohistochemistry studies showed positivity for CD31 and CD34 and negativity for D2-40.Th e histopathologic diagnosis was that of a reactive vascular proliferation -papillary endothelial hyperplasia (Masson's tumor).Th e patient had a favorable postoperative course and no sign of recurrence 6 months after surgery.

DISCUSSION
Although IPEH was initially considered a neoplastic process, nowadays its reactive nature is generally accepted 4 .Th e etiology and pathogenic mechanisms of IPEH are not completely elucidated.It represents an exaggerated endothelial proliferative response to vascular injury 5 .Vascular trauma also generates thrombus formation, infl ammation of the vessel wall and vascular stasis 6 .Many authors argue that thrombosis precedes endothelial proliferation 7 .In addition, fi broblast growth factor (FGF) released by the macrophages attracted at the injury site enhances the proliferation of endothelial cells.Subsequently, the endothelial cells themselves produce FGF and thus the process becomes self-sustained 6 .All these events lead to the formation of papillary projections within the vascular lumen 5 .
IPEH comprises three subtypes 8 .Primary or pure IPEH (type I), which develops within normal blood vessels (usually a vein) is the most frequently encountered.Secondary or mixed IPEH (type II) appears in pre-existing vascular conditions, such as varices, hemangiomas, lymphangiomas, pyogenic granulomas, haematomas, or arteriovenous malformations.Th e undetermined form (type III) is the rarest variant.It is an extravascular form, most often emerging in an organizing haematoma.
IPEH can arise anywhere on the body, but usually aff ects the head and neck area or the extremities 9 .Cases of IPEH located on the oral and lingual mucosa, in the gastrointestinal tract, liver, uterus, heart, intracranially, or in the orbital area have also been reported 10 .IPEH generally presents as a solitary well-circumscribed, round or ovoid, red or purple slow growing papule, nodule or soft-tissue mass, 0.2-5 cm in diameter 11 .Most lesions are asymptomatic, but some patients complain of local pain, especially when IPEH develops in a thrombosed varix 10 .
Preoperative imaging studies help diff erentiate IPEH from other soft tissue tumors.Ultrasonography shows a well-defi ned echogenic mass and can identify blood vessels related to it 12 .Doppler ultrasound detects venous and arterial fl ows within the lesion 13 .Magnetic resonance imaging can also provide useful information 3,13,14 .
Th e histopathologic examination depicts the presence of papillary projections towards the lumen of a dilated and most frequently thrombosed blood vessel.Th e papillary projections display a hyalinized core covered by a monolayer of endothelial cells.Th e endothelial cells that line the papillary growths lack features seen in angiosarcomas, such as atypia, pleomorphism, or increased mitotic activity 15 .Immunohistochemistry studies show positivity for CD31, CD34, SMA, vimentin, and factor VIII-related antigen 6 .CD105 is another marker that can be useful in diff erentiating IPEH from angiosarcoma as it is positive in primary vascular neoplasms 16 .
It is sometimes challenging to diff erentiate IPEH from malignant vascular tumors, especially angiosarcoma, but also Kaposi's sarcoma and rare neoplasms like hemangiopericytoma, epithelioid hemangioendothelioma, and endovascular papillary angioendothelioma (Dabska tumor).Th e absence of atypia of the endothelial cells forming the lesion is a key diff erentiating feature from malignant vascular tumors.Moreover, angiosarcoma is rarely located intravascular, usually invading tissues outside the vessel.Solid areas and necrosis are frequent fi ndings in angiosarcomas 17 .Benign conditions such as hemangiomas, lymphangiomas, hematomas, vascular malformations, pyogenic granulomas, angiolymphoid hyperplasias with eosinophilia, fi bromas, traumatic neuromas, neurofi bromas, schwannomas should also be considered in the diff erential diagnosis of IPEH.
IPEH is treated by complete surgical excision 18 .Wide surgical margins are not necessary.However, recurrences have been reported in the setting of incompletely surgically removed lesions 19 .Malignant transformation of IPEH has not been reported to date.

CONCLUSIONS
Physicians should be aware of this uncommon condition and include it in the diff erential diagnosis of vascular lesions.It is a benign tumor with a very good prognosis.Complete surgical excision is curative.Th erefore, promptly establishing the correct diagnosis helps avoid useless extensive investigations and overtreatment.

Compliance with ethics requirements:
Th e authors declare no confl ict of interest regarding this article.Th e authors declare that all the procedures and experiments of this study respect the ethical standards in the Helsinki Declaration of 1975, as revised in 2008 (5), as well as the national law.Informed consent was obtained from all the patients included in the study.

Figure 1 .
Figure 1.Well circumscribed, 2/1 cm, ovalar, bluish-purple mass with an irregular surface located in the lower left abdominal area.

Figure 2 .
Figure 2. Haematoxylin & eosin stain (A) magnifi cation x 40, (B) magnifi cation x 100 showing a dermal tumor characterized by the presence of a pseudocapsule and multiple pseudocystic spaces of various dimensions occupied by erythrocytes and a homogenous eosinophilic material, that contain papillary projections lined by a monolayer of flat/cubic epithelium surrounding a collagenized core.