Epithelioid Hemangioendothelioma Arising from Interanl Jugular Vein Mimicking Cervical Metastatic Lymphadenopathy.

Epithelioid hemangioendothelioma (EHE) is a relatively rare and moderately aggressive type of vascular tumor. We describe a case of EHE that presented in a 24-year-old woman as a palpable nodule in the left cervical area. Radiological examinations and fine-needle aspiration cytology led to a preliminary diagnosis of metastatic lymphadenopathy with an unknown primary site. However, during surgery, we determined that the nodule was an intra-vascular tumor arising from the left internal jugular vein. The histopathological examination revealed cords of epithelioid endothelial cells distributed in a hyaline stroma, compatible with a diagnosis of EHE.

CASE REPORT

A 24-year-old woman was referred to Chonnam National University Hwasun Hospital with a palpable nodule in the left side of her neck. A nodule had appeared on the site where she had undergone a left thyroidectomy for nodular hyperplasia two years previously. On physical examination, the nodule was found to be hard and painful when pressure was applied, and intermittent swelling of the left upper limb was noted, leading to suspicion of a chronically occluded left subclavian vein. A chest computed tomography (CT) scan showed a 3-cm mass-like lesion in the left supraclavicular area with suspected internal jugular vein invasion (Fig. 1A, B). The diagnosis of the nodule as suspicious for metastatic carcinoma was made by sonography-guided fine needle aspiration cytology. Further testing, including positron emission tomography (PET)/CT, was performed on the assumption that the nodule reflected lymph node metastasis from an unknown primary site. Blood tests and tumor marker levels were normal. On PET/CT, the maximum standardized uptake value was 7.7 in the left supraclavicular area (Fig. 1C). However, no detectable primary site was found. We then planned the surgical excision of the tumor in order to make a definitive histological diagnosis, in accordance with the patient’s desire to remove the tumor. The neck was extended in the supine position, and a left collar incision was performed. Contrary to our expectations, a tumor was found that arose from the internal jugular vein. The incision was extended medially and laterally in order to define the tumor boundaries and adjacent vasculature. The intraluminal mass extended inferiorly into the innominate vein and proximal subclavian vein. After the identification of a chronic innominate vein occlusion, the tumor was resected en bloc with the involved veins following ligation of the innominate, left internal jugular, and left subclavian veins. Unfortunately, no photographs were taken during or after the operation. The patient’s postoperative course was uneventful and no swelling of the left upper limb was observed.

Fig. 1

Chest computed tomography scan shows a 3-cm mass (arrow) in the left supraclavicular area with a markedly narrowed left internal jugular vein. (A) Coronal view. (B) Axial view. (C) A positron emission tomography scan shows increased uptake (maximum standardized uptake value of 7.7) in the left supraclavicular area.

Histopathologically, the tumor was found to be composed of cords and nests of spindled epithelioid cells with intra-cytoplasmic vacuoles in a hyalinized stroma. Immunohistochemical staining for vimentin, CD31, and CD34 was positive (Fig. 2). The surgical margins were free from tumoral invasion. These histopathological and immunohistochemical findings were compatible with the diagnosis of an epithelioid hemangioendothelioma (EHE).

Fig. 2

Histopathological and immunohistochemical findings. (A) Cords and nests of spindled epithelioid cells with intracytoplasmic vacuoles were observed in a hyalinized stroma (H&E, ×100). The tumor cells were immunopositive for (B) vimentin (×200), (C) CD31 (×200), and (D) CD34 (×200).

The patient was referred to the hematology department for adjuvant radiotherapy in order to ensure for better local control, and received a total dose of 60 Gy. Over the course of 18 months of follow-up, she has remained in good condition, with no evidence of local recurrence or distant metastasis.

DISCUSSION

Hemangioendothelioma (HE) refers to a group of vascular neoplasms involving the skin and soft tissues, and is sub-classified into six categories: papillary intralymphatic angioendothelioma (Dabska tumor), retiform HE, kaposiform HE, epithelioid HE, pseudomyogenic HE (epithelioid sarcoma-like HE), and composite HE [1]. Each of these neoplasms shows characteristic histopathological features. According to the current World Health Organization histological classification published in 2002, EHE is defined as ‘an angiocentric vascular tumor with metastatic potential, composed of epithelioid endothelial cells arranged in short cords and nests set in a distinctive myxohyaline stroma.’ EHE develops in either superficial or deep soft tissues such as the skin, liver, lung, or the extremities. Although EHE usually originates from a vessel, it is relatively rare for primary vascular EHE to originate from a large vein or artery, is relatively rare [2]. A few recent reports have described intravascular EHEs arising from large vessels such as the inferior vena cava [2] and azygos vein [3].

EHE occurs in nearly all age groups, with no gender predilection. Most EHEs are asymptomatic, although edema or thrombophlebitis can develop due to their vascular origin [4].

In most cases that have been described, the diagnosis was based on postoperative histological findings, because no specific radiological features led to the suspicion of EHE. In our case, the tumor was first suspected to be metastatic lymphadenopathy with an unknown primary site based on pre-operative radiological findings and fine-needle aspiration cytology, whereas intraoperative findings indicated that the tumor originated in the left internal jugular vein. A definitive diagnosis of EHE must be based on pathological findings. Typical histological findings include nests and cords of epithelioid endothelial cells distributed in a myxohyaline stroma and the presence of intracytoplasmic lumina (vacuoles). The tumor cells can be confirmed by immunohistological studies, in which CD31, CD 34, FLI1, and vimentin are the most commonly used markers [5]. Surgical resection is the preferred treatment modality, and chemotherapy or radiotherapy can be deployed as adjuvant therapies for highly aggressive EHE [6].

EHE is clinically intermediate between hemangioma and conventional angiosarcoma. Although the majority of EHEs show an indolent clinical course, metastasis (20%–30%) and death (10%–20%) have been reported in the literature [7]. Deyrup et al. [8] described the histological and clinical features of 49 cases of EHE that originated in the soft tissue. The overall five-year disease-specific survival rate was 81%, and the metastasis rate was 22%. They suggested that EHE can be classified into two risk groups, with markedly different clinical courses depending on mitotic activity and tumor size.

In summary, we have reported a case of epithelioid HE arising from the left internal jugular vein that was pre-operatively misdiagnosed as metastatic lymphadenopathy with an unknown primary site.