Surgical treatment of a rare case of epithelioid hemangioendothelioma of the azygos vein

Abstract

Epithelioid hemangioendothelioma (EHE) of soft tissues is a rare low-grade vascular tumour, with variable malignancy. Mediastinal localization is exceptional. We report the first case of a radically resected EHE of the azygos vein (AV). A 47-year old man presented to our institution with an asymptomatic incidental neck–chest computerized tomography (CT) evidence of a 3 cm mediastinal mass, resembling a station 4R lymphadenopathy, with rather distinct margins, strictly adjacent to the AV. ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT revealed a SUV max of 2.3. Fiberbronchoscopy with EBUS-trans-tracheal needle aspiration of station 4R yielded nondiagnostic cytology result. A right lateral thoracotomy revealed an ovoidal mediastinal mass originating from the AV, unresectable from it but showing cleavage from the superior vena cava. The mass with the involved AV was resected en bloc by vascular stapler. Histopathology revealed a venous EHE arising from the AV. For the low mitotic rate and small tumour size, no adjuvant therapy was administered. Total body CT scan at one year from surgery shows neither local recurrence, nor distant metastases. EHE should be considered in the differential diagnosis of mediastinal masses in adult patients. After radical removal prognosis is generally favourable, but strict follow-up must be performed because aggressive forms have been described.

INTRODUCTION

Epithelioid hemangioendothelioma (EHE) of soft tissues is a rare vascular tumour, first described by Weiss and Enzinger in 1982, with histologic appearance and clinical behaviour intermediate between that of benign vascular tumours (haemangiomas) and malignant ones (angiosarcomas) [1, 2].

EHEs have also been reported in the lung (so-called intravascular bronchiolar tumours) and liver [2]. When located in soft tissues, EHE occurs in the extremities (65%), head and neck (12%), trunk (8%), mediastinum (8%), genitals (4%) and retroperitoneum (2%) [3].

Mediastinal EHEs originate from medium-sized or large veins: EHEs arising from superior vena cava (SVC) and left brachiocephalic vein have been reported [1, 4–6].

To the best of our knowledge, no cases of EHE of the azygos vein (AV) have been described in the literature. We report the first case of a patient radically surgically treated for a EHE originating from the AV.

CASE REPORT

A 47-year old man presented to our institution with an asymptomatic incidental CT evidence of a mediastinal mass. He underwent total thyroidectomy for goitre about one year before, was on substitutive therapy with l-thyroxine and performed follow-up neck–chest CT scan, showing a suspected mediastinal station 4R lymphadenopathy, 3 cm in diameter, with dishomogeneous structure, rather distinct margins, but not sure cleavage from the SVC, strictly adjacent to the AV (Fig. 1a). ¹⁸F-fluorodeoxyglucose positron emission tomography-(FDG-PET)/CT revealed a slightly increased uptake (SUV max 2.3) of station 4R lymph node (Fig. 1b, c).

Figure 1:

(a) Chest CT scan showing a suspected mediastinal station 4R lymphadenopathy (mass indicated by arrow), 3 cm in diameter, with dishomogeneous structure, rather distinct margins, but not sure cleavage from the SVC, strictly adjacent to the azygos vein (AV); (b, c) ¹⁸F-FDG-PET/CT showing a slightly increased uptake (SUV max 2.3) at the level of mediastinal station 4R lymph node; (d) CT scan at one year from surgery, showing a normal mediastinum without signs of recurrence.

Fiberbronchoscopy was unremarkable, except for a focal convexity of the right tracheal wall, corresponding to station 4R lymph node: EBUS-trans-tracheal needle aspiration was performed, with nondiagnostic cytology result.

After initial VATS exploration, a right lateral thoracotomy revealed a 3 cm ovoidal mediastinal mass, resembling a 4R lymphadenopathy, which was isolated with dissector and ultrasonic scalpel, identifying its origin from the AV, unresectable from it, but showing cleavage from the SVC; the mass was resected en bloc with the involved tract of the AV, stapling the vessel above and below it with Endo-GIA vascular stapler (ATW 35, Ethicon Endo-Surgery Inc., Cincinnati, OH, USA) (Fig. 2a).

Figure 2:

(a) Resected mediastinal mass, resembling a station 4R lymphadenopathy, although in reality originated from the AV, being unresectable from it, but showing cleavage from the SVC; the mass was isolated and resected en bloc with the involved tract of AV by Endo-GIA vascular stapler; (b) haematoxylin–eosin 10×: epithelioid hemangioendothelioma (EHE) arising from the AV (AV wall indicated by black arrow); (c, d) haematoxylin–eosin 200× and 400×: typical pattern of cords and nests of epithelioid endothelial cells in a myxohyaline stroma and the so-called ‘blister’ cells (for intracytoplasmic lumina).

Post-operative course was uneventful; the patient was discharged on the eighth post-operative day.

Definitive histopathological examination revealed a venous EHE arising from the AV, 1 cm in diameter, involving the adjacent 4R lymph node, with a typical pattern of cords and nests of epithelioid endothelial cells in a myxohyaline stroma, low mitotic rate (<2 mitoses/50 HPF) (Fig. 2b–d) and immunohistochemical positivity for CD31, CD34, factor VIII-related antigen and vimentin. Surgical margins were free from tumoural invasion.

The histological diagnosis was confirmed by the Rare Tumours National Net of the Italian National Cancer Institute; for the low mitotic rate and small tumour size, in agreement with this Institution, no adjuvant therapy was administered.

Follow-up was performed at 4 month intervals with total body CT scans and hepatic echography. Post-operative bone scintigraphy resulted negative for metastases. A total body CT scan at one year from surgery showed neither local recurrence, nor distant metastases (Fig. 1d).

DISCUSSION

Nowadays the term epithelioid hemangioendothelioma designates a rare, low-grade malignant neoplasm, with variable malignancy, derived from endothelial cells; its oetiology is unknown and the mediastinal localization is exceptional [1–3, 5, 7, 8].

EHE usually occurs in adulthood (median age 50 years), with no sex predilection [1, 3, 7].

Most patients are asymptomatic [2, 7]; when mediastinal vessels are involved, SVC syndrome or symptoms of compression of surrounding structures may be present [2, 4, 6, 9].

EHEs are generally located in the anterior mediastinal compartment [2, 4, 9], although cases originating in the posterior compartment have been reported [7, 8]. Our case is the first described in the medium mediastinal compartment, arising from the AV.

Radiological features are aspecific; CT scan can show a mediastinal mass with well-defined margins and sometimes calcification [10]. ¹⁸F-FDG-PET/CT can be useful to evaluate metabolic activity of EHEs and search for metastases [10].

Since the mediastinal localization is exceptional, the histological diagnosis is usually established post-operatively [5], as in our patient. In fact, pre-operatively the tumour was thought to be originating from station 4R lymph node, while intra-operatively turned out to be arising from the AV.

Macroscopically, EHE is usually well circumscribed, with a red-to-white cut surface, if arising from a vessel, as in our case (Fig. 2a), and white-grey if not [2, 7].

Classic histologic features include cords and nests of epithelioid endothelial cells within a myxohyaline stroma and the so-called ‘blister’ cells (for intracytoplasmic lumina) [2, 3, 6, 8] (Fig. 2c, d).

Immunohistochemistry confirms the endothelial origin of EHE [2]: tumour cells usually stain positive for endothelial markers factor VIII-related antigen and cytokeratin CD34; can be positive for Ulex europaeus lectin, vimentin and the most specific and sensitive endothelial marker CD31, as in our case [2, 5, 8].

Whenever possible, complete surgical resection is the treatment of choice, usually resulting in long-term survival [2, 5–8]. However, despite a general indolent clinical course, metastases (lung, lymph nodes, liver, bones, retroperitoneum, soft tissues) and death can occur in about 25 and 15% of EHEs, respectively [1, 3]; thus, the WHO has definitely classified EHE as a fully malignant vascular tumour [3].

Radiotherapy and chemotherapy have been tried with limited responses [2, 7, 8].

Some authors have attempted to identify prognostic factors and to stratify risk for mortality of patients with EHEs. Using a combination of both mitotic rate and tumour size, Deyrup and Weiss were able to segregate patients into low-risk and high-risk (tumours displaying >3 mitoses/50 HPF or tumour size >3 cm) groups (indolent vs. aggressive EHEs), with a 5-year disease-specific survival rate of 100 and 59% and metastatic rates of 15 and 32%, respectively [3].

The low mitotic rate and the small tumour size induced us not to administer any adjuvant therapy and to perform only strict radiological follow-up on our patient.

In conclusion, even if rare, EHE should be considered in the differential diagnosis of mediastinal masses in adult patients. It has to be considered as a fully malignant vascular tumour, with variable aggressiveness, mainly depending on mitotic rate and tumour size. After radical removal prognosis is generally favourable, but strict follow-up must be performed, especially for high risk forms with potential aggressive behaviour.

Conflict of interest: none declared.